Update for Advance CAR-T Therapy in Solid Tumors, Clinical Application in Peritoneal Carcinomatosis From Colorectal Cancer and Future Prospects

Abstract

Latest advances in the field of cancer immunotherapy have developed the (Chimeric Antigen Receptor) CAR-T cell therapy. This therapy was first used in hematological malignancies which obtained promising results; therefore, the use of CAR-T cells has become a popular approach for treating non-solid tumors. CAR-T cells consist of T-lymphocytes that are engineered to express an artificial receptor against any surface antigen of our choice giving us the capacity of offering precise and personalized treatment. This leaded to the development of CAR-T cells for treating solid tumors with the hope of obtaining the same result; however, their use in solid tumor and their efficacy have not achieved the expected results. The reason of these results is because solid tumors have some peculiarities that are not present in hematological malignancies. In this review we explain how CAR-T cells are made, their mechanism of action, adverse effect and how solid tumors can evade their action, and also we summarize their use in colorectal cancer and peritoneal carcinomatosis.

Keywords: CAR (chimeric antigen receptor) T cells; colorectal (colon) cancer; immunotherapy; peritoneal carciomatosis; solid tumor.

Figure 1

The structure of a CAR consist of a single chain variable fragment (scFv) that enables the CAR-T cell to recognise the target; a hinge/spacer that binds the scFv to the transmembrane domain and improves the scFv flexibility; a transmembrane domain that act as a link between the extracellular and intracellular portion; Coestimulatory molecules that improvesCAR-T cell efficacy and a CD3z intracelullar domain that activates the CAR-T cell.

Figure 2

First Generation CAR-T cells consist of a scFv region and the CD3ζ intracellular domain. Second-generation CAR-T cells include a costimulatory molecules in the intracellular domain. Third-generation contains two costimulatory molecules. Fourth-generation CAR-T cell or TRUCKs secretes proinflamatory cytokines.

Figure 3

Patient whole blood is extracted and centrifugated in order to obtain the white blood cells. Then T-cells are selected and activated. Afterwards, gene transfer containing the CAR information is inserted into the activated T-cells genome resulting in the creation of CAR-T cells. These cells are expanded and after a quality control, are reinfunsed into the patient.