Cancer Immunotherapy

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Abstract This strategy achieves the goal of targeted T cell activation and anticancer therapeutic protein production by integrating the pro-drug concept with inducible T cell stimulation and gene expression technologies.   Background: A critical issue in advancing current immunotherapies for solid tumors is in developing a strategy that enables T cells to maximize local cancer killing efficacy while minimizing collateral damage on non-tumor sites. Current immunotherapies suffer from off-cancer toxicity and are not effective for solid tumors. Recent developments of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells show great promise for treating cancer. Immune checkpoint inhibitors block the immune checkpoint pathways by targeting key regulators in the pathways (e.g. PD-1/PD-L1, CTLA4) to enhance the immune activity of patients’ effector T cells. Although immune checkpoint blockade has been shown to be effective towards several cancers, systemic administration of these inhibitors has been observed to cause severe immune-related adverse events (irAEs) due to the fact that immune checkpoint pathways also play critical roles in regulating autoimmunity. CAR T cell therapy engineers a patients’ T cells ex vivo to express tailored receptors that can be activated by selected cancer antigens once transferred back to patients. To overcome repressive solid tumor environments and enhance the activity and persistence of CAR T cells, combined therapies including co-administration of immune checkpoint inhibitors or cytokines with CAR T cells have been employed. However, systemic administration of these agents exacerbate the off-tumor toxicities. A new therapeutic strategy that allows for targeted activation of T cells, and simultaneously produces anticancer agents that enhance T cell activity and persistence only in tumor sites, can offer improved immunotherapy.   Description Researchers at the University of New Mexico have developed a novel immunotherapy strategy that addresses limitations of current approaches to offer a significantly improved therapy for solid tumors. This strategy achieves the goal of targeted T cell activation and anticancer therapeutic protein production by integrating the pro-drug concept with inducible T cell stimulation and gene expression technologies. These enhanced conditional T cells should offer superior therapeutic benefits over current immunotherapy approaches.    Advantages Highly customizable and generally applicable for a variety of solid tumors  Capable of being incorporated into current manufacturing procedures of generating CAR T cells Applications in immunotherapy and cancer treatment