Category | Agent | Target | combinational therapies | Tumor type (s) | Phase | References |
---|---|---|---|---|---|---|
Targeting neoantigen depletion | Neo-PV-01 | Personalized neoantigen-based vaccine | Nivolumab | Melanoma NSCLC Bladder Cancer | Phase Ib (NCT02897765) | [98] |
ISA 101 | Synthetic long-peptide HPV-16 vaccine | Nivolumab | HPV-16-positive cancer | Phase II (NCT02426892) | [99] | |
T-VEC | Oncolytic virus | Pembrolizumab | Melanoma | Phase Ib (NCT02263508) | [102] | |
T-VEC | Oncolytic virus | Ipilimumab | Melanoma | Phase II (NCT01740297) | [103] | |
T-VEC | Oncolytic virus | Ipilimumab; Nivolumab; Pembrolizumab | Melanoma | Retrospective | [104] | |
Targeting defects in antigen processing and presentation | LCL161 | The cIAP1/2 antagonist | Anti-PD-L1 and/or anti-CTLA4 | Pancreatic ductal adenocarcinoma | Preclinical | |
Trametinib | The mall molecule MEK inhibitor | Anti-PD-L1 | HNSCC | Preclinical | [106] | |
Chloroquine | Inhibiting autophagy | Anti-PD1 and anti-CTLA4 | PDAC | Preclinical | [107] | |
ASPIRE nanovaccine | Specific pMHC-I, anti-PD1 antibody and B7 are simultaneously anchored by a programmed process | NA | Melanoma Colon carcinoma Lewis lung carcinoma | Preclinical | [108] | |
Targeting IFN‐γ/JAK signaling pathway | BO-112 | A nanoplexed formulation of Poly I: C coupled to polyethylenimine | Anti-PD-L1 | Melanoma | Preclinical | [110] |
BO-112 | A nanoplexed formulation of Poly I: C coupled to polyethylenimine | Pembrolizumab; Nivolumab | Solid tumor | Phase I (NCT02828098) | [111] | |
Overexpression of NLRC5 | Upexpressing NLRC5 | ACT | Melanoma | Preclinical | [112] | |
Targeting alternate ICI activation | F38-2E2 | Anti-TIM-3 antibody | Nivolumab | Lung cancer | Preclinical | [55] |
Ieramilimab | The LAG-3 inhibitor | Spartalizumab | Advanced malignancies | Phase I/II (NCT02460224) | [115] | |
MIH63 | Anti-VISTA antibody | Anti-PD-1 and anti-CTLA-4 | Squamous cell carcinoma | Preclinical | [116] | |
Anti-murine BTLA antibody | Anti-BTLA antibody | Anti-PD-1 | Glioblastoma | Preclinical | [117] | |
Tiragolumab | Anti-TIGIT antibody | Atezolizumab | NSCLC | Phase II (NCT03563716) | [118] | |
Targeting suppressive tumor microenvironment | anti-CD25 antibody | Anti-CD25 antibody | Anti-PD-1 | Sarcoma, colon adenocarcinoma, melanoma, and colorectal carcinoma | Preclinical | [119] |
Mogamulizumab | Anti-CCR4 antibody | Nivolumab | Solid tumors | Phase I (NCT02476123) | [121] | |
PLX3397 | CSF-1R kinase inhibitor | Oncolytic viruses, and anti-PD-1 | Colon cancer | Preclinical | [123] | |
BLZ945 | CSF-1R kinase inhibitor | Anti-PD-1 and anti-PD-L1 | Control spontaneous neuroblastoma | Preclinical | [124] | |
ATRA | Targeting MDSCs | Anti-PD-1 | NSCLC | Preclinical | [125] | |
ATRA | Targeting MDSCs | Ipilimumab | Melanoma | Phase II (NCT02403778) | [126] | |
BMS-211 | Targeting MDSCs | anti-CTLA-4 | Lung carcinoma, colon carcinoma, breast carcinoma and lymphoma | Preclinical | [127] | |
Epacadostat | The IDO1 enzyme inhibitor | Pembrolizumab | Solid tumors | Phase I/II (NCT02178722) | [128] | |
Epacadostat | The IDO1 enzyme inhibitor | Pembrolizumab | Melanoma | Phase III (NCT02752074) | [129] | |
Linrodostat mesylate | The IDO1 enzyme inhibitor | Nivolumab | Bladder cancer | Phase I/II (NCT02658890) | [130] | |
CD39 knockout | Blocking CD39 | anti-PD1 | HCC | Preclinical | [131] | |
Oleclumab | Anti-CD73 monoclonal antibody | Durvalumab | NSCLC | Phase II (NCT05221840) | [132] | |
NIR178 | The A2AR antagonist | Immunotherapy | NSCLC | Phase II (NCT02403193) | [133] | |
TGFβ-blocking | Inhibiting TGFβ | Anti-PD-L1 | Urothelial cancer | Preclinical | [134] | |
Mithramycin | Anti-PD-L1 | Chronic lymphocytic leukemia | Preclinical | [135] | ||
Pegilodecakin | The PEGylated form of IL10 | Pembrolizumab or nivolumab | Solid tumors | Phase IB (NCT02009449) | [136] | |
Targeting epigenetic modification | Decitabine | The DNMT inhibitor | anti-CTLA-4 | Ovarian Cancer | Preclinical | [142] |
Azacitidine | The DNMT inhibitor | Nivolumab | Acute Myeloid Leukemia | Phase II (NCT02397720) | [148] | |
Panobinostat | The HDAC inhibitor | Anti-PD-L1 | Melanoma | Preclinical | [143] | |
Romidepsin | The HDAC inhibitor | Anti-PD-L1 | Lung Adenocarcinoma | Preclinical | [144] | |
HBI-8000 | The HDAC inhibitor | PD-1, PD-L1, or CTLA-4, | Colon carcinoma and B-cell lymphoma | Preclinical | [145] | |
Vorinostat | The HDAC inhibitor | Pembrolizumab | NSCLC | Phase I/Ib (NCT02638090) | [149] | |
Entinostat, | The HDAC inhibitor | Pembrolizumab | Melanoma | Phase Ib/II NCT02437136 | [150] | |
Entinostat | The HDAC inhibitor | Pembrolizumab | NSCLC | Phase Ib/II NCT02437136 | [151] | |
GSK503 | The EZH2 inhibitor | Anti-PD1, anti-CTLA-4 and IL-2 | Melanoma | Preclinical | [146] | |
Targeting gut microbiome Dysbiosis | Bifidobacterium | Regulating gut microbiota | Anti-PD-L1 | Melanoma | Preclinical | [153] |
Bacteroides fragilis | Regulating gut microbiota | Anti-CTLA-4 | Melanoma | Preclinical | [94] | |
Lactobacillus johnsonii, Bifidobacterium pseudolongum, and Olsenella | Regulating gut microbiota | Anti-CTLA-4 | Colorectal cancer, bladder cancer, and melanoma | Preclinical | [154] | |
EDP1503 | Regulating gut microbiota | Pembrolizumab | Solid tumors | Phase I/II (NCT03775850) | [155] | |
MRx0518 | Regulating gut microbiota | Pembrolizumab | Bladder cancer, NSCLC, RCC, and Melanoma | Phase I/II (NCT03637803) | [156] | |
FMT | Regulating gut microbiota | Anti-PD-1 | Epithelial tumors | Preclinical | [89] | |
FMT | Regulating gut microbiota | Nivolumab | Melanoma | Phase I NCT03353402 | [157] | |
FMT | Regulating gut microbiota | Pembrolizumab | Melanoma | Phase II NCT03341143 | [158] | |
Other emerging combination strategies | STING-LNP | Stimulating the STING pathway | Anti-PD-1 | Melanoma | Preclinical | [159] |
MUSIC platform | Stimulating the STING pathway | Anti-PD-1 | Breast cancer | Preclinical | [160] | |
iTPNCs | Activating inflammatory signaling | Anti-CTLA-4 | Melanoma, colon cancer, and breast cancer | Preclinical | [161] | |
177Lu-PSMA-617 | Delivering beta-particle radiation | Pembrolizumab | Prostate cancer | Phase II NCT03805594 | [162] | |
BNT111 | RNA vaccine | Anti-PD-1 | Melanoma | Preclinical | [163] | |
8FNs | Nanovaccine | Anti-PD-1 | Melanoma | Preclinical | [164] |