CAR-M Cells

For the past few years we have been excited by the developments in CAR-T cells and their application to hematological malignancies. We first reported on these in 2016 after several promising trials in various locations. Now T cells have problems with solid malignancies and CAR-T have not seen as much progress there as one would like.

However, recent work reported in Nature on CAR-M cells, macrophages, is quite compelling.They reported:

In vitro, co-culture experiments showed that CAR-Ms induced a pro-inflammatory phenotype in M2 macrophages, activation and maturation of dendritic cells, and recruitment of resting and activated T cells. In vivo, mice with metastatic SKOV3-derived xenografts treated with HER2-targeted CAR-Ms and donor-derived polyclonal (non-specific) T cells showed a better antitumour response than mice treated with CAR-Ms or T cells alone. This synergy is probably due to CAR-M-induced potentiation of T cell antitumour activity. Further experiments showed that CAR-Ms cross-presented intracellular tumour-derived antigens from phagocytosed cells.

 Macrophages are the garbage collectors of the innate immune system. On the one hand they collect, identify and present to the adaptive system all sorts of bad stuff. However on the other hand they are known to protect tumors, called tumor associated macrophages.

This CAR-M cell approach may do two things. First get the good macrophages to attack and help kill off the cancer cells and second, break loose the protective macrophages so tumors can be attacked. This double edged sword may have significant power.