Tumor-specific allogeneic cells for cancer therapy

Abstract

Adoptive cell transfer (ACT) therapy involves transfer of therapeutic lymphocytes to patients mostly for the treatment of cancer and viral infections. One modality to generate therapeutic lymphocytes is to genetically engineer them to express a chimeric antigen receptor (CAR) capable of recognizing the desired target. Current ACT approaches employ the patient's own (syngeneic) lymphocytes, which is both economically and technically challenging. Using foreign (allogeneic) lymphocytes in ACT is problematic because of the severe immunological reaction that occurs between genetically mismatched individuals. However, recently our group has developed a protocol, which allows for safe and effective ACT therapy in a murine model of metastatic disease using allogeneic T cells redirected with a human EGFR2/neuregulin (Her2/neu)-specific CAR. Mild preconditioning of the recipient delayed the rejection of the allogeneic donor T cells such that they had enough time to destroy the tumor, but not enough to cause significant damage to the host. By modulating lymphocyte migration using FTY720, we were actually able to exploit the allogeneic anti-host reaction in order to augment therapeutic benefit while concurrently improving the safety of the treatment. Therefore, we suggest that CAR-based allogeneic ACT therapy could be universally used as a safe and potent ‘off-the-shelf’ treatment for cancer.

Keywords:

• adoptive cell therapy (ACT)
• allogeneic
• cancer
• chimeric antigen receptor (CAR)
• egress
• FTY720
• graft-versus-tumor (GvT)
• graft-verus-host-disease (GvHD)
• hematopoietic cell therapy (HCT)
• Her2/neu
• host-versus-graft (HvG)
• T-body
• tumor