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Table 4 Characteristics and anti-tumor effects of CAR macrophage

From: Targeting macrophages in hematological malignancies: recent advances and future directions

Source of CAR-M Target antigens CAR Structure Generation Stage Preclinical results Refs
J774A.1 CD19 and CD22 CD19 + Megf10
CD19 + FcRV
CD19 + FcRV + PI3K
1st generation Preclinical evaluation CD3ζ, FcRγ and Megf10 intracellular domains demonstrate similar phagocytic activity in vitro and PI3K recruitment domain enhances phagocytosis of whole tumor cells
CD47 mAb enhances the phagocytic activity of CAR-M in vitro;
212
iPSCs CD19 CD19 + 4–1BB + CD3ζ 2nd generation Preclinical evaluation CAR-iMACs demonstrate pro-inflammatory/anti-tumor state in vitro
CAR-iMACs can expand, persist and exert anti-tumor activities in vivo
64
Raw264.7 HER2 HER2 + CD147 1st generation Preclinical evaluation CAR-147 induces MMP expression in vitro and in vivo, but does not enhance phagocytosis of tumor cells
CAR-147 lowers collagen content, increases CD3+ T cell infiltration and inhibits the proliferation of tumor
214
Raw264.7 CCR7 CCL19 + TLR2, TLR4 + TLR6 + MerTk + 4-1BB + CD3ζ 2nd generation Preclinical evaluation In vitro, MerTK (CAR-M) kills and phagocytoses cells more efficiently than CAR-M that has other intracellular domains
CAR-M (MerTK) inhibits the progression of tumors, prolongs survival time, and inhibits tumor metastasis in mice with minimal toxicity
Cancer cells treated with CAR-M (MerTK) exhibit significant CD3+ T cell infiltration, a decrease of PD-L1-positive cells, as well as an increase in pro-inflammatory cytokines
66
Monocytes HER2 HER2 + CD3ζ 2nd generation Phase I Ongoing clinical trials (CT0508) against HER2+ solid tumors Injection of adenoviral vector leads to M1-like macrophages and pro-inflammatory microenvironment in the tumor
An adenovirus-transduced CAR macrophage is capable of cross-presenting tumor-derived antigens and activating T lymphocytes more effectively
An adenovirus-transduced CAR macrophage significantly prolongs survival time and decreases metastasis in mice harboring tumors;
65
Human THP-1 CD19 CD19 + CD3ζ 2nd generation Preclinical evaluation CAR-M enhances antigen-dependent phagocytosis in vitro 65
Murine BMDM ALK ALK + CD8 Hinge + CD28 TM + CD28 CSD + CD3ζ + IFN-γ 3rd generation Preclinical evaluation CAR-M enhances antigen-dependent phagocytosis
CAR-M induces M1 polarization, upregulates antigen presentation, increases T cell activations, and reduces tumor burden
215
Monocytes CD5 Un mRNA engineered Phase I Ongoing clinical trials (MT-101) against PTCL Un Un
  1. Un Unknown