Experimental treatment of colorectal cancer in mice with human T cells electroporated with NKG2D RNA CAR

Aim:Peritoneal metastasis is often present in end-stage neoplastic diseases, including recurrent colorectal cancer and is associated with decreased overall survival. Novel methods are needed.Materials & methods:We constructed first-, second- and third-generation chimeric antigen receptors (CARs) specific for NKG2D ligands and modified human T cells with mRNA electroporation.Results:NKG2D CAR expression was detectable for at least 6 days postelectroporation and mediated efficient cytotoxicity against NKG2DL+ tumor cells, but not NKG2DL-cells. Multiple infusions of the first-generation CAR-T cells into immunodeficient mice bearing established peritoneal colorectal xenografts led to significantly reduced tumor burden.Conclusion:mRNA CAR is an economical way to test new CARs and potentiates controlling on-target/off-tumor toxicity and cytokine storms. The use of NKG2D RNA CARs to treat colorectal peritoneal metastasis warrants further investigation.