A new therapeutic potential for cancers: One CAR with 2 different engines!

Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain. The CARs provide the recognition of target antigen in a MHC-independent manner. CAR-armed T cells may be unable to kill their targets in the absence of co-stimulators like NK cells. On the other hand, CAR-armed NK cells may also be unable to destroy their targets without receiving help signals from Th cells. Thus, if CAR-armed NK cells use together with CAR-armed T cells, NK cells will be aggregated to the tumor site. Thus, not only CAR T cells will obtain the necessary cytokines/costimulators from NK cells, but also other tumor specific T cells will be primed by recognition of tumor specific antigen (TSA) associated with MHC class I. These new specific primed T cells probably combat against tumor cells which have lost their TAAs that CAR-T cells are redirected to them.