Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 3150 2023-02-19 06:58:26 |
2 format Meta information modification 3150 2023-02-20 02:45:44 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Hu, H.; Xia, Q.; Hu, J.; Wang, S. Oncolytic Viruses for the Treatment of Bladder Cancer. Encyclopedia. Available online: (accessed on 17 June 2024).
Hu H, Xia Q, Hu J, Wang S. Oncolytic Viruses for the Treatment of Bladder Cancer. Encyclopedia. Available at: Accessed June 17, 2024.
Hu, Henglong, Qidong Xia, Jia Hu, Shaogang Wang. "Oncolytic Viruses for the Treatment of Bladder Cancer" Encyclopedia, (accessed June 17, 2024).
Hu, H., Xia, Q., Hu, J., & Wang, S. (2023, February 19). Oncolytic Viruses for the Treatment of Bladder Cancer. In Encyclopedia.
Hu, Henglong, et al. "Oncolytic Viruses for the Treatment of Bladder Cancer." Encyclopedia. Web. 19 February, 2023.
Oncolytic Viruses for the Treatment of Bladder Cancer

Bladder cancer is one of the most prevalent cancers. Despite advancements in bladder cancer therapy, new strategies are still required for improving patient outcomes, particularly for those who experienced Bacille Calmette–Guerin failure and those with locally advanced or metastatic bladder cancer. Oncolytic viruses are either naturally occurring or purposefully engineered viruses that have the ability to selectively infect and lyse tumor cells while avoiding harming healthy cells. In light of this, oncolytic viruses serve as a novel and promising immunotherapeutic strategy for bladder cancer. A wide diversity of viruses, including adenoviruses, herpes simplex virus, coxsackievirus, Newcastle disease virus, vesicular stomatitis virus, alphavirus, and vaccinia virus, have been studied in many preclinical and clinical studies for their potential as oncolytic agents for bladder cancer.

bladder cancer oncolytic virus oncolytic viral therapy

1. Introduction

Bladder cancer (BC) is one of the most prevalent malignancies, with approximately 550,000 new cases every year [1][2]. The transurethral resection of bladder tumor (TURBT) and subsequent intravesical therapy (IVT) are the standard treatments for nonmuscle invasive bladder cancer (NMIBC) [3], while for patients with T2-T4a muscle-invasive bladder cancer (MIBC), radical cystectomy is recommended [4]. In addition, systematic chemotherapy is the first-line therapeutic method for metastatistic cancer [5]. While these therapeutic approaches may provide successful curative options, more treatment methods are still required to further improve the outcomes of BC patients, especially those who suffered Bacille Calmette–Guerin (BCG) failure and those with locally advanced or metastatistic BC.
Over the past ten years, immunotherapeutic approaches for the treatment of BC have gained popularity in both preclinical research and clinical practice [6]. One of the immunotherapy drugs is immune checkpoint inhibitors (ICIs). ICIs have gained great success in the treatment of BC, from patients who are unresponsive to BCG to MIBC patients who require systemic neoadjuvant or adjuvant immunotherapy. In addition, oncolytic viruses (OVs) represent another cutting-edge and promising immunotherapeutic strategy for cancer.

2. OVs and Their Antitumor Mechanisms in BC

The use of viruses as potential treatments for many diseases has gained more and more attention [7]. OVs are either naturally occurring or purposefully engineered viruses that have the ability to selectively infect and lyse tumor cells while avoiding causing excessive damage to healthy cells [8][9]. Nonpathogenicity, selectively targeting and killing cancer cells, and the ability to be engineered to express tumor-killing substances are common characteristics of OVs [10]. BC is a good candidate for oncolytic immunotherapy. These are the causes: (1) Intravesical therapy for BC using BCG or other drugs is well established in clinical practice; (2) through intravesical instillation, the BC can be exposed to high virus titers; and (3) the surface area for topical application is increased by the papillary structure of BC [11][12].

2.1. Direct Oncolysis

Malignant cells are particularly vulnerable to OVs infection due to tumor-driver mutations in cancer cells and particular cytokines that these cells produce [13]. For example, numerous tumor cells sustained preferential virus multiplication, which was likely brought on by a deficit in type I interferon’s antiviral signaling [14][15]. In addition, some OVs are molecularly engineered to infect cancer cells specifically [9]. Once infection takes hold, OVs will take control of the tumor cell’s production line for nucleic acids and proteins, preventing the cancer cells from producing enough nucleic acids and proteins to meet their growth requirements and destroying their normal physiological processes [16]. The viruses cause alterations in cell function and ultimately kill and lyse the cancer cells by damaging organelles [17][18][19][20]. Then more OVs are released and spread to nearby cancer cells. OVs may infect healthy cells, but they are unable to proliferate there because these cells have normal antiviral capability and response [9].

2.2. Promoting Antitumor Immunity

The tumor microenvironment (TME) of advanced malignancies is “cold” as lacking anti-tumor immune activity [21]. OVs can directly lyse malignant cells and lead to the release of cell-derived damage-associated molecular patterns (DAMPs), viral pathogen-associated molecular patterns (PAMPs), and soluble tumor-associated antigens (TAAs). These molecules recruit and activate antigen-presenting cells such as dendritic cells (DCs), natural killer (NK) cells, and other immune cells to the infection site. DCs take up soluble tumor antigens and then activate adaptive T cell responses against the tumor at regional lymph nodes. Additionally, enhanced antigen processing and presentation factors and tumor-specific CD8+ T lymphocytes recruitment are brought about by the viral-mediated production of chemokines and type I interferons. These cytotoxic T lymphocytes can recognize and kill both primary and metastatic tumor cells. Interferons’ counterregulatory effects can also increase the production of immunological checkpoint molecules by tumor cells, such as galectin 9 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as programmed cell death 1 ligand 1 (PD-L1) [22]. The immune suppressive TME is finally broken down by OVs to produce an immunologically “hot” TME that promotes the eradication of primary, metastatic, or recurrent tumor cells [23][24][25].

2.3. Inhibition of Intratumor Angiogenesis

Angiogenesis assumes a significant part in tumor growth and development [26]. By directly lysing the vascular endothelial cells, causing microthrombosis and producing anti-angiogenesis viral proteins, some OVs can successfully suppress intratumor angiogenesis and reduce the supply of nutrients and oxygen to cancer cells, thus preventing the proliferation of tumor cells [27][28][29].

3. OVs for BC

Initially, wild-type viruses were used in oncolytic virotherapy (OVT). To improve the effectiveness of treatment, second-generation OVs were built on genetically engineered viruses. Third-generation OVs are “armed viruses” that have been cloned with immune stimulatory or toxic genes such as granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-2 to accelerate resistant antitumor immunity and increase tumor destruction [30][31]. A wide diversity of viruses have been investigated for their potential to act as oncolytic agents for BC, including adenoviruses, herpes simplex virus (HSV), Coxsackievirus, alphavirus, vaccinia virus, Newcastle disease virus (NDV), and vesicular stomatitis virus (VSV), et al. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64].

3.1. Adenovirus

Adenovirus is the most explored and studied OVs in BC. As a double-stranded DNA virus, it has an icosahedral capsid and infects the cell through Coxsackie and adenovirus receptors [63]. To increase antitumor effectiveness and cancer cell selectivity, many genetically modified adenoviruses have been created. In 2002, Zhang et al. published their pioneering work in this area [58]. They engineered Uroplakin II (UPII) promoter into adenovirus type 5 to create an attenuated replication-competent adenovirus variant termed CG8840. In contrast to normal cells, CG8840 was highly selective (10,000:1) and capable of efficiently replicating in and eliminating BC cells. Additionally, the injection of CG8840 intravenously and intratumorally to RT4 human BC xenografts significantly slowed the growth of the tumors [58]. Then, Ramesh et al. constructed CG0070, a serotype 5 adenovirus that contains the cDNA for human GM-CSF [49]. GM-CSF is well known for being a strong inducer of specific and persistent anticancer immunity. Several BC models were used in in vitro and in vivo experiments and confirmed the GM-CSF production, cytotoxicity, selective replication, and antitumor effectiveness of CG0070 [49]. Results from preclinical studies led researchers to assess the safety, pharmacokinetics, and anticancer activity of CG0070 in 35 patients with NMIBC. According to the phase I trial, intravesical therapy is safe and generated considerable anticancer activity [65]. Additionally, the overall CR rate for BCG-unresponsive NMIBC patients is 47% according to the phase II study’s 6-month interim results. The CR rate for patients with pure CIS was 58%, and it was 50% in BC patients whose tumors incorporating CIS [66]. In an orthotopic model, Wang et al. discovered that the direct intravesical instillation of AxdAdB-3, a oncolytic adenovirus with the deletion of E1B-55KD and mutant E1A, dramatically slowed the growth of the bladder tumor [56]. Lichtenegger et al. demonstrated that the intratumoral delivery of XVir-N-31, a YB-1-selective adenovirus, significantly inhibited tumor development and caused higher immunogenic cell death (ICD) in BC cells than wild-type adenovirus [42]. Furthermore, Lu and his colleagues evaluated the teratogenic toxicity of BC-specific adenovirus Ad-PSCAE-UPII- E1A-AR on mice and determined that it was safe in pregnant mice and had no discernible effects on the development of F1 mice [45]. There are numerous other OVs that have been studied preclinically in BC, for example, Ad-MK-E1a [53], Ad.9OC [57], Ad5F35/MKp-E1 [34], Ad/PSCAE/UPII/E1A [60][61][67], RGD-hTERT-TRAIL [62], AdLCY [44]. Most of the results are encouraging.

3.2. Herpesvirus

HSV is a double-stranded DNA virus with enclosed virions that has the ability to remain latent in host cell neurons [68][69]. HSV-1 is quite prevalent; about 67% of people worldwide have ever been exposed to it [70]. Many different oncolytic HSVs (T-VEC, G207, HSV1716, NV1020, HF10, et al.) have been designed and developed to treat a variety of malignant tumors, including BC [69][71][72]. However, the main issue with applying HSV-1 in clinical practice is that it is neurotropic, which could increase the risk of neurovirulent side effects when used in clinical settings. To decrease this risk, recombinant HSV-1s were developed by deleting the neurovirulent genes such as the diploid 134.5 genes and thymidine kinase (TK). G207 is a genetically engineered OV based on wild-type HSV-1. The deletion of γ134.5, which results in greatly decreased neurovirulence, is one of G207’s distinguishing characteristics [73]. NV1020 is another HSV-1 mutant with a loss of 700-bp in the TK gene [72][73]. All four human BC cell lines and MBT-2 cells were susceptible to infection, internal replication, and lysing by both viruses. In vivo research showed that these viruses were efficient at reducing tumor burden in syngeneic C3h/Hej mice with a single intravesical instillation and even more effective with multiple instillations [72]. In 2005, the effectiveness of a HSV-1 mutant HF10 for regulating the proliferation of human and mouse BC cells was examined by Kohno et al. in vitro and in vivo [40]. They discovered that HF10 replicated effectively in MBT-2 and T24 BC cells and caused significant cell lysis. In mice with disseminated peritoneal and BC models, the treatment of HF10 markedly increased survival rates and lengthened survival durations [40]. There are also some similar HSV-1 mutants such as NV1066. According to Mullerad et al., NV1066 synergistically increased MMC’s cytotoxicity for BC cell lines (KU19-19 and SKUB) [46]. However, these deletions unavoidably diminish the oncolytic effectiveness and replication efficiency of HSV-1 [74]. Therefore, Zhang et al. designed a recombinant virus and tried to regulate the expression of genes essential for replication with endogenous microR143 and microR124. They found that the miR143/124-regulated HSV-1 could restrict viral replication in neurons and normal bladder cells while killing BC cells with high potency. Thus, it is possible to maintain the full viral genome for the greatest oncolytic potency while maintaining the highest level of safety by translationally regulating the expression of essential viral genes [63].
Pseudorabies virus (PrV), a neurotropic herpesvirus, infects a variety of hosts but is nonpathogenic for humans [75][76]. Shiau et al. generated YP2 virus, a Glycoprotein E/TK-defective PrV mutant carrying both Glycoproteins D and HSV-1 TK genes under the transcriptional control of the HER-2/neu promoter [52]. In MIBC, there has been evidence of HER-2/neu overexpression, which is associated with worse clinical outcomes and increased metastases [77][78]. It enhances cancer cell survival, invasion, and angiogenesis, leading to increased cancer metastases and resistance to various cancer therapies [78]. Researchers found that YP2 selectively lysed HER-2/neu-overexpressing mouse and human BC cells. In addition, YP2 significantly inhibited the growth of the MBT-2 bladder tumor in mice [52].
Recently, Joo et al. constructed an oncolytic virus from HSV-2 termed FusOn-H2 that targets cancer cells selectively by activating the signaling pathway of Ras [38]. In an orthotopic murine BC mode, they assessed the anticancer activity of FusOn-H2. They found that in the majority of the animals, two moderately dosed intravesical instillations of the virus completely eliminated the tumors. Additionally, FusOn-H2 triggered a potent systemic immune response to the native tumor antigens created by tumor cells. They also compared FusOn-H2 with an oncolytic HSV-1 (Baco-1) and discovered that FusOn-H2 had considerably higher anticancer efficacy [38]. According to their findings, FusOn-H2 may act as an effective oncolytic drug for orthotopic BC.

3.3. Coxsackievirus

A naturally occurring common cold RNA virus known as Coxsackievirus A21 (CVA21) has demonstrated specific oncolytic activity in many tumors [79]. In a panel of human BC cell lines, Pandha et al. studied CVA21-induced cytotoxicity and discovered a variety of sensitivities that were largely correlated with the expression of the viral receptor ICAM-1 [32]. They also discovered the expression of the ICD determinant calreticulin and the release of HMGB-1 in CVA21-treated BC cell lines, which indicated that CVA21 could induce immunogenic apoptosis [32].
Based on these findings, a phase I/II trial (CANON, NCT02316171) was conducted to investigate the therapeutic potential of CVA21 (CAVATAK) for NMIBC. This trial included 15 NMIBC patients who were candidates for TURBT and evaluated the feasibility, safety, and biological effects of escalating intravesical doses of CAVATAK, either alone or combined with MMC. The production of tumor inflammation and bleeding after intravesical installations of CAVATAK served as clinical evidence of the drug’s activity. CAVATAK induced significant inflammatory alterations within NMIBC tissue whether it was used alone or in combination with MMC. One patient had a complete resolution of the tumor. Regardless of whether a patient was getting viral or combination therapy, no severe toxicities were reported [80].

3.4. Vesicular Stomatitis Virus

VSV, a negative-sense RNA virus with an envelope, can selectively replicate in IFN-resistant cancer cells [14][81]. IFN resistance favors tumor growth over normal cells but impairs the cancer’s ability to fight viruses [82][83]. This vulnerability of tumor cells is present in many malignancies [84]. A study assessed 57 cancer cell lines and found that 47 of them were sensitive to VSV oncolysis [85].
Hadaschik et al. treated four human BC cell lines (KU-7, UM-UC3, MGH-U3, and RT4) with either a mutant d51M variant (AV3) or wild-type VSV [35]. They discovered that the IFN-nonresponsive and more aggressive BC cell lines UM-UC3 and KU-7 were more frequently destroyed by AV3 and wild-type VSV, whereas IFN-responsive RT4 and MGH-U3 BC cells were less vulnerable. Intravesically administering type VSV and AV3 both dramatically reduced the growth of the KU-7 tumor in mice by 98% (wild-type) and 90% (AV3). These discoveries provide preliminary evidence supporting the intravesical use of VSV in NMIBC patients, particularly those with IFN resistance [33]. Furthermore, they found that type I interferon receptor down-regulation made BC cells more susceptible to VSV-induced cell death [64].
Recently, Rangsitratkul et al. armed VSVd51 with GM-CSF [50], treated human and mouse BC cells or spheroids with VSVd51-m/hGM-CSF, and observed the enhanced release of immunogenic factors and anger signals. Additionally, the intravenous administration of the OV increased survival and decreased tumor volume in MB49 BC-bearing C57Bl/6 mice and promoted the activation of bladder-infiltrating and peripheral effector immune cells [50]. These results suggest that the engineered VSVd51-hGM-CSF may be a promising OV for BC.

3.5. Alphavirus

Oncolytic alphaviruses have seen investigated to treat different types of malignancies such as brain cancers, leukemia, melanomas, lymphomas, and BC [86]. A Getah-like alphavirus strain with positive single-strand RNA called M1 was discovered in China’s Hainan Province [87]. The M1 virus has the ability to specifically reproduce in cancer cells, which allows it to eliminate them without seriously affecting healthy organs [88]. The zinc-finger antiviral protein (ZAP) gene regulates M1’s replication, which has a powerful and selective anticancer effect. According to a study of cancer tissue banks, 61% of BC tissue has low levels of ZAP, which suggests that M1 has a wide range of potential applications [17]. M1 caused endoplasmic reticulum stress, which led to apoptosis [17] Additionally, M1 can make cancer cells more sensitive to them when the cyclic adenosine monophosphate pathway is activated [89].
Orthotopic MIBC mice given M1 treatment had significantly slower tumor growth and longer survival times [37]. M1 has more potent antitumor effects than the first-line chemotherapeutic drug cisplatin. Decreased Ki-67 signals and enhanced cleaved-caspase-3 signal, which are indicators of cell proliferation and death, respectively, were seen in treated tumors [37]. This indicates that M1 is a novel oncolytic agent for MIBC. The M1 virus is susceptible to the antiviral effects of coiled-coil-domain-containing 6. And knocking down it increased M1’s oncolytic effects through endoplasmic reticulum stress-mediated apoptosis [43].

3.6. Newcastle Disease Virus

The NDV genome is a nonsegmented, single-stranded, negative-sense RNA, and it is a pleomorphic enveloped virus with a diameter of 200–300 nm [90]. Despite the possibility of modest transient flu-like symptoms or conjunctivitis, NDV is typically not harmful to people [30]. Numerous human cancers with pathogenic (Ulster, PV701, and MTH-68/H) and nonpathogenic (73-T, LaSota, HUJ, and Hitchner-B1) viral strains have shown that NDV has oncolytic potential [30]. As early as 1992, the cytolytic activity 73-T was determined on six human tumor cell lines including BC cells (HCV29T). The researchers found that the intratumoral injection of 73-T caused full tumor regression in mice and that the drug selectively and effectively lysed BC cells [51]. Infected human and mouse cells with NDV cause ICD, the activation of innate immune pathways, and the elevation of major histocompatibility complex and PD-L1, according to a recent discovery by Anton Oseledchyk [47]. Intratumoral therapy with NDV enhanced immune infiltration and effected a change from an inhibitory to an effector T cell phenotype in both treated and untreated BC tumors [47]. Improvements in local and distant tumor control and overall survival have been seen when intratumoral NDV was combined with systemic programmed cell death protein 1 (PD-1) or CTLA-4 inhibition [47]. These results support more clinical studies combining intratumoral NDV treatment with systemic immunomodulatory drugs.

3.7. Reovirus

Reovirus is a nonenveloped, double-stranded (ds) RNA virus with 2 concentric icosahedral protein capsids, measuring around 85 nm in diameter [91]. Although reovirus can be found in the human respiratory and gastrointestinal tracts, it is not known to be harmful. Reovirus’s oncolytic abilities seem to be somewhat reliant on Ras signaling. Ras transformation also influences many phases of the viral life cycle, which helps to increase reovirus oncolysis [92]. Reovirus was shown to have the ability to destroy rat AY-27 BC cell lines and human BC cell lines (RT-112 and MGH-U3) in a preclinical investigation by Kilani et al. [39]. Using an orthotopic bladder tumor model, Hanel et al. reported the first intravesical oncolytic reovirus for the treatment of NMIBC [36]. When compared with the BCG group, the reovirus group’s side effects were fewer. Reovirus treatment significantly increased tumor-free survival compared with BCG or standard saline treatment in animals [36].

3.8. Vaccinia Virus

The double-stranded DNA virus vaccinia virus (VV), which has a genomic length of roughly 190 kb, offers a number of features that make it a promising OVT agent [93][94][95]: (1) VV has been crucial to the effectiveness of the smallpox vaccine. VV has a long history of usage in people with success, which implies that it is a secure oncolytic drug. (2) VV has a vast genome; a significant amount of foreign DNA can be inserted without affecting the virus’s ability to reproduce. VV stays in the cell cytoplasm throughout the infectious cycle, in contrast to other groups of DNA viruses [94][95]. VV has been studied in a variety of human malignancies including BC [94][95][96]. The F4L gene, which codes for the virus’s homolog of the ribonucleotide reductase’s cell-cycle-regulated small subunit, is a crucial part of VV virulence, and viral strains lacking the F4L gene exhibit in vivo attenuation [48]. By muting F4L, Potts et al. created a new oncolytic VV that selectively replicates in BCG-resistant BC cells (AY-27) and xenografted human RT112-luc orthotopic BC mice, significantly inhibiting tumor growth without producing any apparent side effects [48]. Their research offers patients with BC who are resistant to BCG a potentially effective treatment.


  1. Richters, A.; Aben, K.K.H.; Kiemeney, L. The global burden of urinary bladder cancer: An update. World J. Urol. 2020, 38, 1895–1904.
  2. Safiri, S.; Kolahi, A.A.; Naghavi, M.; Global Burden of Disease Bladder Cancer, C. Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990–2019: A systematic analysis for the global burden of disease study 2019. BMJ Glob. Health 2021, 6, e004128.
  3. Babjuk, M.; Burger, M.; Capoun, O.; Cohen, D.; Comperat, E.M.; Dominguez Escrig, J.L.; Gontero, P.; Liedberg, F.; Masson-Lecomte, A.; Mostafid, A.H.; et al. European association of urology guidelines on non-muscle-invasive bladder cancer (ta, t1, and carcinoma in situ). Eur. Urol. 2022, 81, 75–94.
  4. Cathomas, R.; Lorch, A.; Bruins, H.M.; Comperat, E.M.; Cowan, N.C.; Efstathiou, J.A.; Fietkau, R.; Gakis, G.; Hernandez, V.; Espinos, E.L.; et al. The 2021 updated european association of urology guidelines on metastatic urothelial carcinoma. Eur. Urol. 2022, 81, 95–103.
  5. Powles, T.; Bellmunt, J.; Comperat, E.; De Santis, M.; Huddart, R.; Loriot, Y.; Necchi, A.; Valderrama, B.P.; Ravaud, A.; Shariat, S.F.; et al. Bladder cancer: Esmo clinical practice guideline for diagnosis, treatment and follow-up. Ann. Oncol. 2022, 33, 244–258.
  6. Esfahani, K.; Roudaia, L.; Buhlaiga, N.; Del Rincon, S.V.; Papneja, N.; Miller, W.H., Jr. A review of cancer immunotherapy: From the past, to the present, to the future. Curr. Oncol. 2020, 27, S87–S97.
  7. Ylosmaki, E.; Cerullo, V. Design and application of oncolytic viruses for cancer immunotherapy. Curr. Opin. Biotechnol. 2020, 65, 25–36.
  8. Chaurasiya, S.; Fong, Y.; Warner, S.G. Oncolytic virotherapy for cancer: Clinical experience. Biomedicines 2021, 9, 419.
  9. Jhawar, S.R.; Thandoni, A.; Bommareddy, P.K.; Hassan, S.; Kohlhapp, F.J.; Goyal, S.; Schenkel, J.M.; Silk, A.W.; Zloza, A. Oncolytic viruses-natural and genetically engineered cancer immunotherapies. Front. Oncol. 2017, 7, 202.
  10. Maroun, J.; Munoz-Alia, M.; Ammayappan, A.; Schulze, A.; Peng, K.W.; Russell, S. Designing and building oncolytic viruses. Future Virol. 2017, 12, 193–213.
  11. Potts, K.G.; Hitt, M.M.; Moore, R.B. Oncolytic viruses in the treatment of bladder cancer. Adv. Urol. 2012, 2012, 404581.
  12. Shen, Z.; Shen, T.; Wientjes, M.G.; O’Donnell, M.A.; Au, J.L. Intravesical treatments of bladder cancer: Review. Pharm. Res. 2008, 25, 1500–1510.
  13. Coffey, M.C.; Strong, J.E.; Forsyth, P.A.; Lee, P.W. Reovirus therapy of tumors with activated ras pathway. Science 1998, 282, 1332–1334.
  14. Stojdl, D.F.; Lichty, B.; Knowles, S.; Marius, R.; Atkins, H.; Sonenberg, N.; Bell, J.C. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat. Med. 2000, 6, 821–825.
  15. Guse, K.; Dias, J.D.; Bauerschmitz, G.J.; Hakkarainen, T.; Aavik, E.; Ranki, T.; Pisto, T.; Sarkioja, M.; Desmond, R.A.; Kanerva, A.; et al. Luciferase imaging for evaluation of oncolytic adenovirus replication in vivo. Gene Ther. 2007, 14, 902–911.
  16. Garmaroudi, G.A.; Karimi, F.; Naeini, L.G.; Kokabian, P.; Givtaj, N. Therapeutic efficacy of oncolytic viruses in fighting cancer: Recent advances and perspective. Oxid. Med. Cell. Longev. 2022, 2022, 3142306.
  17. Lin, Y.; Zhang, H.; Liang, J.; Li, K.; Zhu, W.; Fu, L.; Wang, F.; Zheng, X.; Shi, H.; Wu, S.; et al. Identification and characterization of alphavirus m1 as a selective oncolytic virus targeting zap-defective human cancers. Proc. Natl. Acad. Sci. USA 2014, 111, E4504–E4512.
  18. Ramamurthy, N.; Pathak, D.C.; D’Silva, A.L.; Batheja, R.; Mariappan, A.K.; Vakharia, V.N.; Chellappa, M.M.; Dey, S. Evaluation of the oncolytic property of recombinant newcastle disease virus strain r2b in 4t1 and b16-f10 cells in-vitro. Res. Vet. Sci. 2021, 139, 159–165.
  19. Li, Q.; Oduro, P.K.; Guo, R.; Li, R.; Leng, L.; Kong, X.; Wang, Q.; Yang, L. Oncolytic viruses: Immunotherapy drugs for gastrointestinal malignant tumors. Front. Cell. Infect. Microbiol. 2022, 12, 921534.
  20. Yang, L.; Gu, X.; Yu, J.; Ge, S.; Fan, X. Oncolytic virotherapy: From bench to bedside. Front. Cell Dev. Biol. 2021, 9, 790150.
  21. Hemminki, O.; Dos Santos, J.M.; Hemminki, A. Oncolytic viruses for cancer immunotherapy. J. Hematol. Oncol. 2020, 13, 84.
  22. Bommareddy, P.K.; Shettigar, M.; Kaufman, H.L. Integrating oncolytic viruses in combination cancer immunotherapy. Nat. Rev. Immunol. 2018, 18, 498–513.
  23. Wang, L.; Chard Dunmall, L.S.; Cheng, Z.; Wang, Y. Remodeling the tumor microenvironment by oncolytic viruses: Beyond oncolysis of tumor cells for cancer treatment. J. Immunother. Cancer 2022, 10, 1805–1808.
  24. Davola, M.E.; Mossman, K.L. Oncolytic viruses: How “lytic” must they be for therapeutic efficacy? Oncoimmunology 2019, 8, e1581528.
  25. Coffin, R.S. Oncolytic immunotherapy: An emerging new modality for the treatment of cancer. Ann. Oncol. 2016, 27, 1805–1808.
  26. Lugano, R.; Ramachandran, M.; Dimberg, A. Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cell. Mol. Life Sci. 2020, 77, 1745–1770.
  27. Breitbach, C.J.; Arulanandam, R.; De Silva, N.; Thorne, S.H.; Patt, R.; Daneshmand, M.; Moon, A.; Ilkow, C.; Burke, J.; Hwang, T.H.; et al. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013, 73, 1265–1275.
  28. Breitbach, C.J.; Paterson, J.M.; Lemay, C.G.; Falls, T.J.; McGuire, A.; Parato, K.A.; Stojdl, D.F.; Daneshmand, M.; Speth, K.; Kirn, D.; et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol. Ther. 2007, 15, 1686–1693.
  29. Angarita, F.A.; Acuna, S.A.; Ottolino-Perry, K.; Zerhouni, S.; McCart, J.A. Mounting a strategic offense: Fighting tumor vasculature with oncolytic viruses. Trends Mol. Med. 2013, 19, 378–392.
  30. Tayeb, S.; Zakay-Rones, Z.; Panet, A. Therapeutic potential of oncolytic newcastle disease virus: A critical review. Oncolytic Virotherapy 2015, 4, 49–62.
  31. Cattaneo, R.; Miest, T.; Shashkova, E.V.; Barry, M.A. Reprogrammed viruses as cancer therapeutics: Targeted, armed and shielded. Nat. Rev. Microbiol. 2008, 6, 529–540.
  32. Annels, N.E.; Arif, M.; Simpson, G.R.; Denyer, M.; Moller-Levet, C.; Mansfield, D.; Butler, R.; Shafren, D.; Au, G.; Knowles, M.; et al. Oncolytic immunotherapy for bladder cancer using coxsackie A21 virus. Mol. Ther. Oncolytics 2018, 9, 1–12.
  33. Cao, W.; Tian, J.; Li, C.; Gao, Y.; Liu, X.; Lu, J.; Wang, Y.; Wang, Z.; Svatek, R.S.; Rodriguez, R. A novel bladder cancer-specific oncolytic adenovirus by cd46 and its effect combined with cisplatin against cancer cells of car negative expression. Virol. J. 2017, 14, 149.
  34. Gotoh, A.; Nagaya, H.; Kanno, T.; Tagawa, M.; Nishizaki, T. Fiber-substituted conditionally replicating adenovirus ad5f35 induces oncolysis of human bladder cancer cells in in vitro analysis. Urology 2013, 81, 920.e7–920.e11.
  35. Hadaschik, B.A.; Zhang, K.; So, A.I.; Fazli, L.; Jia, W.; Bell, J.C.; Gleave, M.E.; Rennie, P.S. Oncolytic vesicular stomatitis viruses are potent agents for intravesical treatment of high-risk bladder cancer. Cancer Res. 2008, 68, 4506–4510.
  36. Hanel, E.G.; Xiao, Z.; Wong, K.K.; Lee, P.W.; Britten, R.A.; Moore, R.B. A novel intravesical therapy for superficial bladder cancer in an orthotopic model: Oncolytic reovirus therapy. J. Urol. 2004, 172, 2018–2022.
  37. Hu, C.; Liu, Y.; Lin, Y.; Liang, J.K.; Zhong, W.W.; Li, K.; Huang, W.T.; Wang, D.J.; Yan, G.M.; Zhu, W.B.; et al. Intravenous injections of the oncolytic virus m1 as a novel therapy for muscle-invasive bladder cancer. Cell Death Dis. 2018, 9, 274.
  38. Joo, K.J.; Li, H.; Zhang, X.; Lerner, S.P. Therapeutic effect on bladder cancer with a conditionally replicating oncolytic virus derived from type ii herpes simplex virus. Bladder Cancer 2015, 1, 81–90.
  39. Kilani, R.T.; Tamimi, Y.; Hanel, E.G.; Wong, K.K.; Karmali, S.; Lee, P.W.; Moore, R.B. Selective reovirus killing of bladder cancer in a co-culture spheroid model. Virus Res. 2003, 93, 1–12.
  40. Kohno, S.; Luo, C.; Goshima, F.; Nishiyama, Y.; Sata, T.; Ono, Y. Herpes simplex virus type 1 mutant hf10 oncolytic viral therapy for bladder cancer. Urology 2005, 66, 1116–1121.
  41. Li, S.; Wang, F.; Zhai, Z.; Fu, S.; Lu, J.; Zhang, H.; Guo, H.; Hu, X.; Li, R.; Wang, Z.; et al. Synergistic effect of bladder cancer-specific oncolytic adenovirus in combination with chemotherapy. Oncol. Lett. 2017, 14, 2081–2088.
  42. Lichtenegger, E.; Koll, F.; Haas, H.; Mantwill, K.; Janssen, K.P.; Laschinger, M.; Gschwend, J.; Steiger, K.; Black, P.C.; Moskalev, I.; et al. The oncolytic adenovirus xvir-n-31 as a novel therapy in muscle-invasive bladder cancer. Hum. Gene Ther. 2019, 30, 44–56.
  43. Liu, Y.; Li, K.; Zhu, W.B.; Zhang, H.; Huang, W.T.; Liu, X.C.; Lin, Y.; Cai, J.; Yan, G.M.; Qiu, J.G.; et al. Suppression of ccdc6 sensitizes tumor to oncolytic virus m1. Neoplasia 2021, 23, 158–168.
  44. Lu, C.S.; Hsieh, J.L.; Lin, C.Y.; Tsai, H.W.; Su, B.H.; Shieh, G.S.; Su, Y.C.; Lee, C.H.; Chang, M.Y.; Wu, C.L.; et al. Potent antitumor activity of oct4 and hypoxia dual-regulated oncolytic adenovirus against bladder cancer. Gene Ther. 2015, 22, 305–315.
  45. Lu, K.; Wang, F.; Ma, B.; Cao, W.; Guo, Q.; Wang, H.; Rodriguez, R.; Wang, Z. Teratogenic toxicity evaluation of bladder cancer-specific oncolytic adenovirus on mice. Curr. Gene Ther. 2021, 21, 160–166.
  46. Mullerad, M.; Bochner, B.H.; Adusumilli, P.S.; Bhargava, A.; Kikuchi, E.; Hui-Ni, C.; Kattan, M.W.; Chou, T.C.; Fong, Y. Herpes simplex virus based gene therapy enhances the efficacy of mitomycin c for the treatment of human bladder transitional cell carcinoma. J. Urol. 2005, 174, 741–746.
  47. Oseledchyk, A.; Ricca, J.M.; Gigoux, M.; Ko, B.; Redelman-Sidi, G.; Walther, T.; Liu, C.; Iyer, G.; Merghoub, T.; Wolchok, J.D.; et al. Lysis-independent potentiation of immune checkpoint blockade by oncolytic virus. Oncotarget 2018, 9, 28702–28716.
  48. Potts, K.G.; Irwin, C.R.; Favis, N.A.; Pink, D.B.; Vincent, K.M.; Lewis, J.D.; Moore, R.B.; Hitt, M.M.; Evans, D.H. Deletion of f4l (ribonucleotide reductase) in vaccinia virus produces a selective oncolytic virus and promotes anti-tumor immunity with superior safety in bladder cancer models. EMBO Mol. Med. 2017, 9, 638–654.
  49. Ramesh, N.; Ge, Y.; Ennist, D.L.; Zhu, M.; Mina, M.; Ganesh, S.; Reddy, P.S.; Yu, D.C. CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor--armed oncolytic adenovirus for the treatment of bladder cancer. Clin. Cancer Res. 2006, 12, 305–313.
  50. Rangsitratkul, C.; Lawson, C.; Bernier-Godon, F.; Niavarani, S.R.; Boudaud, M.; Rouleau, S.; Gladu-Corbin, A.O.; Surendran, A.; Ekindi-Ndongo, N.; Koti, M.; et al. Intravesical immunotherapy with a gm-csf armed oncolytic vesicular stomatitis virus improves outcome in bladder cancer. Mol. Ther. Oncolytics 2022, 24, 507–521.
  51. Reichard, K.W.; Lorence, R.M.; Cascino, C.J.; Peeples, M.E.; Walter, R.J.; Fernando, M.B.; Reyes, H.M.; Greager, J.A. Newcastle disease virus selectively kills human tumor cells. J. Surg. Res. 1992, 52, 448–453.
  52. Shiau, A.L.; Lin, Y.P.; Shieh, G.S.; Su, C.H.; Wu, W.L.; Tsai, Y.S.; Cheng, C.W.; Lai, M.D.; Wu, C.L. Development of a conditionally replicating pseudorabies virus for her-2/neu-overexpressing bladder cancer therapy. Mol. Ther. 2007, 15, 131–138.
  53. Terao, S.; Shirakawa, T.; Kubo, S.; Bishunu, A.; Lee, S.J.; Goda, K.; Tsukuda, M.; Hamada, K.; Tagawa, M.; Takenaka, A.; et al. Midkine promoter-based conditionally replicative adenovirus for targeting midkine-expressing human bladder cancer model. Urology 2007, 70, 1009–1013.
  54. Van der Poel, H.G.; Molenaar, B.; van Beusechem, V.W.; Haisma, H.J.; Rodriguez, R.; Curiel, D.T.; Gerritsen, W.R. Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer. J. Urol. 2002, 168, 266–272.
  55. Wang, H.; Cai, Z.; Yang, F.; Luo, J.; Satoh, M.; Arai, Y.; Li, D. Enhanced antitumor efficacy of integrin-targeted oncolytic adenovirus axdadb3-f/rgd on bladder cancer. Urology 2014, 83, 508.e13–508.e19.
  56. Wang, H.; Satoh, M.; Abe, H.; Sunamura, M.; Moriya, T.; Ishidoya, S.; Saito, S.; Hamada, H.; Arai, Y. Oncolytic viral therapy by bladder instillation using an e1a, e1b double-restricted adenovirus in an orthotopic bladder cancer model. Urology 2006, 68, 674–681.
  57. Wu, C.L.; Shieh, G.S.; Chang, C.C.; Yo, Y.T.; Su, C.H.; Chang, M.Y.; Huang, Y.H.; Wu, P.; Shiau, A.L. Tumor-selective replication of an oncolytic adenovirus carrying oct-3/4 response elements in murine metastatic bladder cancer models. Clin. Cancer Res. 2008, 14, 1228–1238.
  58. Zhang, J.; Ramesh, N.; Chen, Y.; Li, Y.; Dilley, J.; Working, P.; Yu, D.C. Identification of human uroplakin ii promoter and its use in the construction of CG8840, a urothelium-specific adenovirus variant that eliminates established bladder tumors in combination with docetaxel. Cancer Res. 2002, 62, 3743–3750.
  59. Zhao, G.Z.; Tan, W.L.; Zheng, S.B.; Wu, Y.D.; Xie, Y.; Zhu, W.H. cytotoxic effect of oncolytic virus combined with mitomycin against human bladder cancer cells in vitro and in vivo. Nan Fang Yi Ke Da Xue Xue Bao 2006, 26, 1623–1625, 1628.
  60. Wang, L.; Zhang, Y.; Zhao, J.; Xiao, E.; Lu, J.; Fu, S.; Wang, Z. Combination of bladder cancer-specific oncolytic adenovirus gene therapy with cisplatin on bladder cancer in vitro. Tumour Biol. 2014, 35, 10879–10890.
  61. Zhang, H.; Wang, F.; Mao, C.; Zhang, Z.; Fu, S.; Lu, J.; Zhai, Z.; Li, R.; Li, S.; Rodriguez, R.; et al. Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells. Int. J. Radiat. Biol. 2017, 93, 174–183.
  62. Yang, Y.; Xu, H.; Shen, J.; Yang, Y.; Wu, S.; Xiao, J.; Xu, Y.; Liu, X.Y.; Chu, L. Rgd-modifided oncolytic adenovirus exhibited potent cytotoxic effect on car-negative bladder cancer-initiating cells. Cell Death Dis. 2015, 6, e1760.
  63. Zhang, K.X.; Matsui, Y.; Lee, C.; Osamu, O.; Skinner, L.; Wang, J.; So, A.; Rennie, P.S.; Jia, W.W. Intravesical treatment of advanced urothelial bladder cancers with oncolytic hsv-1 co-regulated by differentially expressed micrornas. Gene Ther. 2016, 23, 460–468.
  64. Zhang, K.X.; Matsui, Y.; Hadaschik, B.A.; Lee, C.; Jia, W.; Bell, J.C.; Fazli, L.; So, A.I.; Rennie, P.S. Down-regulation of type i interferon receptor sensitizes bladder cancer cells to vesicular stomatitis virus-induced cell death. Int. J. Cancer 2010, 127, 830–838.
  65. Burke, J.M.; Lamm, D.L.; Meng, M.V.; Nemunaitis, J.J.; Stephenson, J.J.; Arseneau, J.C.; Aimi, J.; Lerner, S.; Yeung, A.W.; Kazarian, T.; et al. A first in human phase 1 study of CG0070, a gm-csf expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. J. Urol. 2012, 188, 2391–2397.
  66. Packiam, V.T.; Lamm, D.L.; Barocas, D.A.; Trainer, A.; Fand, B.; Davis, R.L., 3rd; Clark, W.; Kroeger, M.; Dumbadze, I.; Chamie, K.; et al. An open label, single-arm, phase ii multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Urol. Oncol. 2018, 36, 440–447.
  67. Shi, J.; Fu, S.; Wang, L.; Tao, Y.; Rodriguez, R.; Wang, Z. Lentivirus-mediated p21/waf-1 short hairpin rna enhances the cytotoxic effects and replicative potential of a bladder cancer-specific oncolytic adenovirus in vitro. Anticancer Drugs 2017, 28, 88–96.
  68. Hong, B.; Sahu, U.; Mullarkey, M.P.; Kaur, B. Replication and spread of oncolytic herpes simplex virus in solid tumors. Viruses 2022, 14, 118.
  69. Watanabe, D.; Goshima, F. Oncolytic virotherapy by hsv. Adv. Exp. Med. Biol. 2018, 1045, 63–84.
  70. Looker, K.J.; Magaret, A.S.; May, M.T.; Turner, K.M.; Vickerman, P.; Gottlieb, S.L.; Newman, L.M. Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS ONE 2015, 10, e0140765.
  71. Ma, W.; He, H.; Wang, H. Oncolytic herpes simplex virus and immunotherapy. BMC Immunol. 2018, 19, 40.
  72. Cozzi, P.J.; Malhotra, S.; McAuliffe, P.; Kooby, D.A.; Federoff, H.J.; Huryk, B.; Johnson, P.; Scardino, P.T.; Heston, W.D.; Fong, Y. Intravesical oncolytic viral therapy using attenuated, replication-competent herpes simplex viruses g207 and nv1020 is effective in the treatment of bladder cancer in an orthotopic syngeneic model. FASEB J. 2001, 15, 1306–1308.
  73. Mineta, T.; Rabkin, S.D.; Yazaki, T.; Hunter, W.D.; Martuza, R.L. Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat. Med. 1995, 1, 938–943.
  74. Shah, A.C.; Price, K.H.; Parker, J.N.; Samuel, S.L.; Meleth, S.; Cassady, K.A.; Gillespie, G.Y.; Whitley, R.J.; Markert, J.M. Serial passage through human glioma xenografts selects for a deltagamma134.5 herpes simplex virus type 1 mutant that exhibits decreased neurotoxicity and prolongs survival of mice with experimental brain tumors. J. Virol. 2006, 80, 7308–7315.
  75. Enquist, L.W.; Husak, P.J.; Banfield, B.W.; Smith, G.A. Infection and spread of alphaherpesviruses in the nervous system. Adv. Virus Res. 1998, 51, 237–347.
  76. Tan, L.; Yao, J.; Yang, Y.; Luo, W.; Yuan, X.; Yang, L.; Wang, A. Current status and challenge of pseudorabies virus infection in china. Virol. Sin. 2021, 36, 588–607.
  77. Jimenez, R.E.; Hussain, M.; Bianco, F.J., Jr.; Vaishampayan, U.; Tabazcka, P.; Sakr, W.A.; Pontes, J.E.; Wood, D.P., Jr.; Grignon, D.J. Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: Prognostic significance and comparative analysis in primary and metastatic tumors. Clin. Cancer Res. 2001, 7, 2440–2447.
  78. Su, W.P.; Tu, I.H.; Hu, S.W.; Yeh, H.H.; Shieh, D.B.; Chen, T.Y.; Su, W.C. Her-2/neu raises shp-2, stops ifn-gamma anti-proliferation in bladder cancer. Biochem. Biophys. Res. Commun. 2007, 356, 181–186.
  79. Bradley, S.; Jakes, A.D.; Harrington, K.; Pandha, H.; Melcher, A.; Errington-Mais, F. Applications of coxsackievirus A21 in oncology. Oncolytic Virotherapy 2014, 3, 47–55.
  80. Annels, N.E.; Mansfield, D.; Arif, M.; Ballesteros-Merino, C.; Simpson, G.R.; Denyer, M.; Sandhu, S.S.; Melcher, A.A.; Harrington, K.J.; Davies, B.; et al. Phase i trial of an icam-1-targeted immunotherapeutic-coxsackievirus A21 (CVA21) as an oncolytic agent against non muscle-invasive bladder cancer. Clin. Cancer Res. 2019, 25, 5818–5831.
  81. Liu, G.; Cao, W.; Salawudeen, A.; Zhu, W.; Emeterio, K.; Safronetz, D.; Banadyga, L. Vesicular stomatitis virus: From agricultural pathogen to vaccine vector. Pathogens 2021, 10, 1092.
  82. Snell, L.M.; McGaha, T.L.; Brooks, D.G. Type i interferon in chronic virus infection and cancer. Trends Immunol. 2017, 38, 542–557.
  83. Geoffroy, K.; Bourgeois-Daigneault, M.C. The pros and cons of interferons for oncolytic virotherapy. Cytokine Growth Factor Rev. 2020, 56, 49–58.
  84. Zitvogel, L.; Galluzzi, L.; Kepp, O.; Smyth, M.J.; Kroemer, G. Type i interferons in anticancer immunity. Nat. Rev. Immunol. 2015, 15, 405–414.
  85. Stojdl, D.F.; Lichty, B.D.; tenOever, B.R.; Paterson, J.M.; Power, A.T.; Knowles, S.; Marius, R.; Reynard, J.; Poliquin, L.; Atkins, H.; et al. Vsv strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell 2003, 4, 263–275.
  86. Lundstrom, K. Oncolytic alphaviruses in cancer immunotherapy. Vaccines 2017, 5, 9.
  87. Wen, J.S.; Zhao, W.Z.; Liu, J.W.; Zhou, H.; Tao, J.P.; Yan, H.J.; Liang, Y.; Zhou, J.J.; Jiang, L.F. Genomic analysis of a chinese isolate of getah-like virus and its phylogenetic relationship with other alphaviruses. Virus Genes 2007, 35, 597–603.
  88. Cai, J.; Yan, G. The identification and development of a novel oncolytic virus: Alphavirus m1. Hum. Gene Ther. 2021, 32, 138–149.
  89. Li, K.; Zhang, H.; Qiu, J.; Lin, Y.; Liang, J.; Xiao, X.; Fu, L.; Wang, F.; Cai, J.; Tan, Y.; et al. Activation of cyclic adenosine monophosphate pathway increases the sensitivity of cancer cells to the oncolytic virus m1. Mol. Ther. 2016, 24, 156–165.
  90. Ganar, K.; Das, M.; Sinha, S.; Kumar, S. Newcastle disease virus: Current status and our understanding. Virus Res. 2014, 184, 71–81.
  91. Muller, L.; Berkeley, R.; Barr, T.; Ilett, E.; Errington-Mais, F. Past, present and future of oncolytic reovirus. Cancers 2020, 12, 3219.
  92. Gong, J.; Sachdev, E.; Mita, A.C.; Mita, M.M. Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity. World J. Methodol. 2016, 6, 25–42.
  93. Colamonici, O.R.; Domanski, P.; Sweitzer, S.M.; Larner, A.; Buller, R.M. Vaccinia virus b18r gene encodes a type i interferon-binding protein that blocks interferon alpha transmembrane signaling. J. Biol. Chem. 1995, 270, 15974–15978.
  94. Truong, C.S.; Yoo, S.Y. Oncolytic vaccinia virus in lung cancer vaccines. Vaccines 2022, 10, 240.
  95. Guo, Z.S.; Lu, B.; Guo, Z.; Giehl, E.; Feist, M.; Dai, E.; Liu, W.; Storkus, W.J.; He, Y.; Liu, Z.; et al. Vaccinia virus-mediated cancer immunotherapy: Cancer vaccines and oncolytics. J. Immunother. Cancer 2019, 7, 6.
  96. Al Yaghchi, C.; Zhang, Z.; Alusi, G.; Lemoine, N.R.; Wang, Y. Vaccinia virus, a promising new therapeutic agent for pancreatic cancer. Immunotherapy 2015, 7, 1249–1258.
Subjects: Surgery
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , ,
View Times: 280
Revisions: 2 times (View History)
Update Date: 20 Feb 2023
Video Production Service