Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Mao, Xiaoqi; Xu, Jin; Wang, Wei; Liang, Chen; Hua, Jie; Liu, Jiang; Zhang, Bo; Meng, Qingcai; Yu, Xianjun; Shi, Si

doi:10.1186/s12943-021-01428-1

Molecular Cancer

Table 3 Multiple preclinical or clinical studies and related drugs for CAF-targeted depletion immunotherapy

From: Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Drugs	Classification	Combination therapy	therapeutic effects	Cancer models	Preclinical/Clinical	Refs
SynCon DNA vaccine	FAP-targeted DNA vaccine	Tumor antigen-specific DNA vaccine, Cyclo-phosphamide	Breaks immune tolerance and promotes antitumor immunity	Lung and breast cancer	Preclinical	[295,296,297]
DC-shA20-FAP-TRP2	FAP-targeted DC vaccine compound	Anti-CAFs therapies	Elicits broad-based T-cell responses and anticancer activities	Melanoma	Preclinical	[298, 299]
AdC68-mFAP vaccine	FAP-targeted adenoviral vectors vaccines	None	Enhances T-cell responses and inhibits tumor proliferation	Melanoma	Preclinical	[300]
FAP-specific CAR T cells	FAP-targeted adoptive T cell therapy	Gemcitabine	Enhances antitumor immune responses and restricts tumor proliferation, angio-genesis, ECM remodeling and chemoresistance	Pancreatic and lung cancer	Preclinical	[301]
ASGPAGPA-A12ADT/ DSGETGP-A12ADT	FAP-activated prodrugs	Thapsigargin	Enhances the specific antitumor effect of drugs with less systemic toxicity	Breast and prostate cancer	Preclinical	[302]
Val-boroPro (talabostat)	FAP-targeted inhibitory small-molecules	Cisplatin	Suppresses tumor growth and invasion and prolongs patients’ survival	Colorectal cancer, Melanoma	Phase II	[303, 304]
RG7386 (FAP-DR5 Antibody)	FAP-targeted inhibitory antibody	Irinotecan/ Doxorubicin	Induces cell-apoptosis and enhances antitumor immune responses	Lung, renal, colorectal, and breast cancer	Preclinical	[305]
αFAP-PE38	FAP-targeted inhibitory immunotoxins	Paclitaxel, Anti-CAF vaccine	Inhibits tumor angiogenesis and increases antitumor activities	Breast Cancer	Preclinical	[306, 307]
Bispecific scFv`FAP/CD105-IL liposomes	FAP-targeted compound liposomes	Doxorubicin/Trastuzumab	Enhances the cytotoxicity of Doxorubicin and cell interaction	Fibrosarcoma	Preclinical	[308]
Cellax (Docetaxel-conjugate nanoparticles)	α-SMA-targeted nanoparticles	None	Enhances anti-stromal effect and inhibits tumor metastasis and angiogenesis	PDAC and breast cancer	Preclinical	[309, 310]
Crenolanib	PDGFR-targeted inhibitor	None	Not available	Gastro-intestinal stromal tumor	Phase III	[311]

Diverse CAF-targeted depleting immunotherapeutic strategies in preclinical/clinical studies
FAP fibroblast activation protein, DC dendritic cell, shA20 A20-specific shRNA, TRP2 tyrosine-related protein 2, AdC68 adenoviral vector of chimpanzee serotype 68, CAR T cells chimeric antigen receptor T cells, CAFs cancer-associated fibroblasts, ECM extracellular matrix, DR5 death receptor 5, PE38 a genetically engineered form of the Pseudomonas exotoxin, scFv single chain antibody fragment, CD105 cluster of differentiation 105, IL interleukin, α-SMA alpha smooth muscle actin, PDAC pancreatic ductal adenocarcinoma, PDGFR platelet-derived growth factor receptor

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ISSN: 1476-4598

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