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Involvement of the immune system in biological therapies specifically targeting tumor microenvironment has been suggested. Substantial advancement in the treatment of malignant tumors utilizing immune cells, most importantly T cells that play a key role in cell-mediated immunity, have led to success in clinical trials.
Target |
Drug INN (Brand Name) |
Cancer Type |
Current Status |
Ref. |
---|---|---|---|---|
Antibodies Based |
||||
CTLA-4 |
Ipilimumab (Yervoy) |
Melanoma (2011) and Renal cell carcinoma (2018) |
FDA approved |
|
Multiple cancers |
Phase I-III |
[52] |
||
Tremelimumab (Imjudo) |
Antineoplastic; liver cancer |
FDA approved |
||
PD-1 |
Nivolumab (Opdivo) |
Melanoma (2014), NSCLC (2015), and Renal (2018) cancers, Hodgkin lymphoma |
FDA approved |
|
Multiple cancers |
Phase I-III |
[52] |
||
Pembrolizumab (Keytruda) |
Melanoma (2014), Various (2015) |
FDA approved |
[56] |
|
Multiple cancers |
Phase I-III |
[52] |
||
MED10680 |
Multiple cancers |
Phase I |
[52] |
|
AMP-224 |
Multiple cancers |
Phase I |
[52] |
|
Pidilizumab |
Multiple cancers |
Phase I-II |
[52] |
|
Cemiplimab (Libtayo) |
Cutaneous squamous-cell carcinoma (2018) |
FDA approved |
||
PD-L1 |
Atezolizumab (Tecentriq) |
Bladder, NSCLC (2016), and TNBC (2019), hepatocellular carcinoma, HCC (2020) |
FDA approved |
[52] |
Avelumab (Bavencio) |
Urothelial Carcinoma (2017), Merkel Cell Carcinoma (2017), Renal carcinoma (2019) |
FDA approved |
[57] |
|
MED14736 |
Multiple cancers |
Phase III |
[52] |
|
Avelumab (Bavencio) |
Merkel cell carcinoma (2017), Rena (2019), Urothelial carcinoma (2020) |
FDA approved |
[57] |
|
BMS-936559 |
Multiple cancers |
Phase I |
[52] |
|
Durvalumab (IMFINZI) |
Bladder Cancer (2017), NSCLC (2018) |
FDA approved |
||
LAG-3 |
IMP321 |
Multiple cancers |
Phase I |
[52] |
BMS-986016 |
Multiple cancers |
Phase I |
[52] |
|
Relatlimab (Opdualag) |
Melanoma (2022) |
FDA approved |
[53] |
|
VEGF |
Bevacizumab |
Colorectal (2004), NSCLC (2006, 2018), Renal (2009), Cervical (2014), Glioblastoma (2009), and Ovarian (2018) Cancers |
FDA approved |
|
VEGF-A, Ang-2 |
Faricimab (Vabysmo) |
wAMD, DME |
FDA approved |
[53] |
VEGFR2 |
Ramucirumab (Cyramza) |
Gastric cancer (2014), NSCLC (2020), HCC (2019) |
FDA approved |
|
EGFR |
Cetuximab |
Colorectal cancer (CRC) (2004, 2012) and Head and neck squamous cell carcinoma (2006, 2011) |
FDA approved |
|
Necitumumab (Portrazza) |
NSCLC (2015) |
FDA approved |
||
Panitumumab (Vectibix) |
Colorectal Cancer (2006) |
FDA approved |
[59] |
|
PDGFRα |
Olaratumab (Lartruvo) |
Soft-tissue sarcoma (2016) |
FDA approved |
[59] |
HER2 |
Pertuzumab (Perjeta) |
HER2-positive Breast cancer (2012) |
FDA approved |
|
Trastuzumab (Herceptin) |
HER2-positive Breast cancer (1998) |
FDA approved |
||
Ado-trastuzumab emtansine (Kadcyla) |
HER2-Breast cancer (2013) |
FDA approved |
[59] |
|
Fam-trastuzumab deruxtecan (Enhertu) |
HER2-positive Breast cancer (2019) |
FDA approved |
[59] |
|
Trastuzumab tucatinib |
HER2-positive Breast cancer (2020) |
FDA approved |
[57] |
|
CCR4 |
Mogamulizumab (Poteligeo) |
Cutaneous T cell lymphoma (2018) |
FDA approved |
[59] |
CD20 |
Obinutuzumab (Gazyva) |
Chronic lymphocytic leukemia (2013), follicular lymphoma (2017) |
FDA approved |
|
Ofatumumab (Arzerra) |
Chronic lymphocytic leukemia (2014) |
FDA approved |
||
Rituximab (MabThera, Rituxan) |
B-Cell Lymphoma (1997) |
FDA approved |
[59] |
|
Ibritumomab tiuxetan (Zevalin) |
NHL (2004) |
FDA approved |
||
tositumomab Iodine-131 (Bexxar) |
NHL (2003) |
FDA approved |
[59] |
|
Ublituximab |
Chronic lymphocytic leukemia, CLL, non-Hodgkin’s lymphoma) and non-cancer (multiple sclerosis) |
Phase III |
||
CD33 |
Gemtuzumab ozogamicin (Mylotarg) |
Acute myeloid leukemia (2000) |
FDA approved |
|
CD30 |
Brentuximab vedotin (Adcetris) |
Hodgkin’s lymphoma and Anaplastic large-cell lymphoma (2011) |
FDA approved |
|
CD79B |
Polatuzumab vedotin (Polivy) |
Diffuse large B-cell lymphoma (2019) |
FDA approved |
|
CD22 |
Inotuzumab ozogamicin (BESPONSA) |
Acute lymphoblastic leukemia (2017) |
FDA approved |
|
Moxetumomab pasudotox (Lumoxiti) |
Hairy-cell leukemia (2018) |
FDA approved |
||
CD19 |
Inebilizumab (Uplizna) |
Neuromyelitis optica and neuromyelitis optica spectrum disorders (2022) |
FDA approved |
[53] |
CD19, CD3 |
Blinatumomab (Blincyto) |
Acute lymphoblastic leukemia (2014) |
FDA approved |
|
TROP2 |
Sacituzumab govitecan (Trodelvy) |
TNBC (2020) |
FDA approved |
|
CD3 |
Muromonab-CD3 (Orthoclone Okt3) |
Reversal of kidney transplant rejection (1986) |
FDA approved |
[60] |
CD3, BCMA |
Teclistamab (TECVAYLI) |
Multiple myeloma (2022) |
FDA approved |
[53] |
gp100, CD3 |
Tebentafusp (KIMMTRAK) |
Metastatic uveal melanoma (2022) |
FDA approved |
[53] |
CD30, CD3 |
Mosunetuzumab (Lunsumio) |
Follicular lymphoma (2022) |
FDA Review |
[53] |
CD38 |
Daratumumab (Darzalex) |
Multiple Myeloma (2015) |
FDA approved |
|
Isatuximab (Sarclisa) |
Multiple Myeloma (2020) |
FDA approved |
||
GD2 |
Dinutuximab (Qarziba; Unituxin) |
Neuroblastoma (2015) |
FDA approved |
|
Nectin-4 |
Enfortumab Vedotin (Padcev) |
Bladder cancer (2019), Urothelial cancer (2022) |
FDA approved |
Small Drugs Based |
||||
---|---|---|---|---|
Target |
Drug INN (Brand Name) |
Cancer Type |
Current Status |
Ref. |
EGFR |
Gefitinib |
NSCLC (2015) |
FDA approved |
|
Erlotinib HCl (Tarceva) |
NSCLC (2004) |
FDA approved |
[63] |
|
Osimertinib mesylate |
NSCLC (2020) |
FDA approved |
||
Dacomitinib (Vizimpro) |
EGFR-mutated NSCLC (2018) |
FDA approved |
||
Mobocertinib succinate (Exkivity) |
EGFR exon 20-mutated NSCLC (2021) |
FDA approved |
[63] |
|
HER2 |
Tucatinib (Tukysa) |
HER2-positive breast cancer (2020) |
FDA approved |
|
EGFR, HER2, and HER4 |
Neratinib maleate (Nerlynx) |
HER2-overexpressed breast cancer (2017) |
FDA approved |
[63] |
Afatinib dimaleate (Gilotrif) |
Metastatic NSCLC with EGFR exon 19 deletion or exon 21 (L858R) mutation (2013) |
FDA approved |
[63] |
|
PARP |
Olaparib (Lynparza) |
Advanced BRCA-mutated ovarian cancer (2020) |
FDA approved |
|
Rucaparib camsylate (Rubraca) |
BRCA-positive ovarian cancer (2016) |
FDA approved |
||
Niraparib tosylate (Zejula) |
Epithelial ovarian, fallopian tube, or primary peritoneal cancer (2017) |
FDA approved |
[63] |
|
PDGFRα |
Avapritinib (Ayvakit) |
metastatic gastrointestinal stromal tumor (GIST) with platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutations (2020) |
FDA approved |
|
Multitarget TKI (VEGFRs, PDGFRα/β, CSF1R, KIT, and FLT3) |
Sunitinib malate (Sutent) |
Imatinib-resistant GIST and advanced RCC (2013) |
FDA approved |
|
Multitarget TKI (RET, VEGFRs, KIT, PDGFRα/β, FGFR1/2, RAF1, BRAF, and BRAFV600E) |
Regorafenib (Stivarga) |
Metastatic colorectal cancer (2012) |
FDA approved |
|
Multitarget TKI (VEGFR2/3, PDGFRβ, FLT3, KIT, RAF1, and BRAF) |
Sorafenib toylate (Nexavar) |
Advanced RCC (2005) |
FDA approved |
[63] |
Multitarget TKI (VEGFRs, PDGFRα/β, FGFR1/2, KIT) |
Pazopanib HCl (Votrient) |
Metastatic RCC (2009) |
FDA approved |
[63] |
Multitarget TKI (VEGFRs, FGFRs, PDGFRα, RET, and KIT) |
Lenvatinib mesylate (Lenvima) |
Thyroid cancer (2015) |
FDA approved |
[63] |
Multitarget TKI (VEGFR2/3, EGFR, and RET) |
Vandetanib (Caprelsa) |
Unresectable or metastatic medullary thyroid cancer (2011) |
FDA approved |
|
Multitarget TKI (VEGFRs, MET, RET, FLT3, KIT, TIE2, and AXL) |
Cabozantinib S-malate (Cometriq) |
Progressive, metastatic medullary thyroid cancer (2012) |
[63] |
|
VEGFRs |
Axitinib (Inlyta) |
Advanced RCC (2012) |
FDA approved |
|
Tivozanib HCl (Fotivda) |
Advanced RCC (2021) |
FDA approved |
[63] |
|
mTOR |
Everolimus (Afinitor) |
Advanced RCC (2009), HER2-negative breast cancer after failure of treatment with letrozole or anastrozole (2012), nonfunctional neuroendocrine tumors of gastrointestinal or lung origin with unresectable, locally advanced, or metastatic disease (2016) |
FDA approved |
|
Temsirolimus (Torisel) |
Advanced RCC (2007) |
FDA approved |
[63] |