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 |