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Cell-Penetrating Peptides Applications
Since their identification over twenty-five years ago, the plethora of cell-penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid in length peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger than themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor-specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell-activated forms. These methods are currently being used to image integrin-expressing tumors, breast cancer cells, human histiocytic lymphoma and protease-secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, antitumor antibodies and nanoparticles can be functionally attached to these peptides, leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue.
2. Clinical Trials Using CPPs as Cancer Therapeutics
|Sponsor||ClinicalTrials.govIdentifier||Study Stage||CPP Employed||Cancer Targeted||Drug Employed with CPP||Study Size|
|Aileron Therapeutics ||NCT02264613||Phase 1—Completed
|ALRN-6924||Solid tumor, lymphoma, and peripheral T-cell lymphoma||ALRN-6924—alone and in combination withpalbociclib||149|
|Aileron Therapeutics ||NCT02909972||Phase 1—Completed||ALRN-6924||Acute myeloid leukemia, and advanced myelodysplastic syndrome||ALRN-6924—alone and in combination with cytarabine||55|
|Aileron Therapeutics ||NCT03725436||Phase 1||ALRN-6924||Advanced, metastatic or unresectable solid tumors||ALRN-6924—in combination with paclitaxel||45|
|Aileron Therapeutics ||NCT03654716||Phase 1||ALRN-6924||Pediatric leukemia, pediatric brain tumor, pediatric solid tumor, pediatric lymphoma||ALRN-6924—alone or in combination with cytarabine for patients with leukemia||69|
|Aileron Therapeutics ||NCT04022876||Phase 1a—Completed
|ALRN-6924||Small cell lung cancer||Phase 1b—ALRN-6924 with topotecan
Phase 2—topotecan alone and in combination with ALRN-6924
|Cancer Research UK ||NCT03486730||Phase 1
|BT1718||Advanced solid tumors, non-small cell lung cancer, non-small cell lung sarcoma, and esophageal cancer||BT1718—alone||130|
|CDG Therapeutics and Dr. Tapas K. Das Gupta ||NCT00914914||Phase 1—Completed||P28||Refractory solid tumors||P28—alone||15|
|Pediatric Brain Tumor Consortium/National Cancer Institute (NCI) ||NCT01975116||Phase 1—Completed||P28||Recurrent or progressive central nervous system tumors||P28—alone||18|
|Institut Curie ||NCT04733027||Phase 1||PEP-010||Metastatic solid tumor cancer||PEP-010—alone
PEP-010—in combination with paclitaxel
|Amal Therapeutics ||NCT04046445||Phase 1a—Completed
|ATP128||Stage IV colorectal cancer||ATP128—alone and in combination with BI 754091||32|
The entry is from 10.3390/pharmaceutics13060890
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- Aileron Therapeutics. ALRN-6924 in Patients with Advanced Solid Tumors or Lymphomas; National Library of Medicine: Bethesda, MD, USA, 2014; NCT02264613 (ClinicalTrials.gov Identifier).
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- Aileron Therapeutics. ALRN-6924 and Paclitaxel in Treating Patients with Advanced, Metastatic, or Unresectable Solid Tumors; National Library of Medicine: Bethesda, MD, USA, 2018; NCT03725436 (ClinicalTrials.gov Identifier).
- Aileron Therapeutics. Phase 1 Study of the Dual MDM2/MDMX Inhibitor ALRN-6924 in Pediatric Cancer; National Library of Medicine: Bethesda, MD, USA, 2018; NCT03654716 (ClinicalTrials.gov Identifier).
- Aileron Therapeutics. A Study of ALRN-6924 for the Prevention of Topotecan-induced Myelosuppression During Treatment for Small Cell Lung Cancer; National Library of Medicine: Bethesda, MD, USA, 2019; NCT04022876 (ClinicalTrials.gov Identifier).
- Cancer Research, UK. BT1718 in Patients with Advanced Solid Tumours; National Library of Medicine: Bethesda, MD, USA, 2018; NCT03486730 (ClinicalTrials.gov Identifier).
- Das Gupta, T.K. Safety Study of a Cell Penetrating Peptide (p28) to Treat Solid Tumors That Resist Standard Methods of Treatmen; National Library of Medicine: Bethesda, MD, USA, 2009; NCT00914914 (ClinicalTrials.gov Identifier).
- Pediatric Brain Tumor Consortium. p28 in Treating Younger Patients with Recurrent or Progressive Central Nervous System Tumors; National Library of Medicine: Bethesda, MD, USA, 2013; NCT01975116 (ClinicalTrials.gov Identifier).
- Institut Curie. First-in-human Phase I to Evaluate PEP-010 as Single Agent and in Combination with Paclitaxel (CleverPeptide); National Library of Medicine: Bethesda, MD, USA, 2021; NCT04733027 (ClinicalTrials.gov Identifier).
- Amal Therapeutics. Phase 1b Study to Evaluate ATP128, With or Without BI 754091, in Patients with Stage IV Colorectal Cancer (KISIMA-01); National Library of Medicine: Bethesda, MD, USA, 2019; NCT04046445 (ClinicalTrials.gov Identifier).