A Novel Universal CAR T Cells Immunotherapy For The Treatment Of Solid Tumors

Recently, remarkable clinical responses were observed in patients treated with engineered T cells, establishing immunotherapy as one of the most promising clinical approaches for cancer. Nonetheless, for unknown reasons, therapies using engineered T cells are currently effective only with hematological malignancies, and treated patient often suffer a relapse. Furthermore, the lack of identified tumor-specific antigens limits the clinical use of this therapy and often results in on-target, off-site toxicity. Therefore, an urgent need remains to develop treatments capable of eradicating solid tumors, which feature a higher safety profile and do not depend exclusively on the host T-cell repertoire.

In an unpublished study, we have recently discovered a novel subset of CD4⁺ T cells that directly kill tumor cells coated with antibodies. These cells express the high affinity Fcg receptor (FcgRI), which enables them to bind coated tumor cells and secrete lytic granules resulting in remarkable tumor lysis. Recognition of the tumor also involves engagement of their T cell receptor (TCR), thus providing another layer of specificity. Importantly, we were able to recapitulate the cytotoxic capacities of that population in conventional CD8⁺ T cells by co-infecting them with FcgRI and the FcR common gamma chain. Indeed, these FcgRI engineered T cells exerted remarkable killing capabilities of solid tumors, upon incubation with antibodies. Unlike chimeric-antigen receptor T (CAR-T) cells, which require chaining the targeting receptor with each tumor, this technology can be applied to treat a wide range of cancers by using clinically-approved antibodies, or antibodies with a high safety profile that have failed in phase III clinical trials.