New targets and technologies for CAR-T cells.

Abstract

Immunotherapy with gene-engineered chimeric antigen receptor (CAR)-T cells has curative potential in advanced malignancies and undergoes a surging preclinical and clinical development. Here, we present a selection of new targets and technologies that illustrate the progress that is being made with the aspiration to make CAR-T cell therapy a universally applicable and effective treatment in cancer medicine. There is a rich pipeline of new target antigens for CAR-T cells in hematology and oncology that are rated based on uniformity but also stability of expression on tumor cells under therapeutic pressure. New technologies in CAR-T cell engineering are directed at neutralizing inhibitory ligands and factors in the tumor microenvironment, preventing CAR-T cell exhaustion and enhancing selectivity for tumor cells with 'smart' CAR designs. The manufacture of CAR-T cells using virus-free protocols is anticipated to reduce supply-chain complexity and to improve patient access. CD19 CAR-T cell therapy is an approved treatment for B-cell leukemia and -lymphoma and considering the current 'target and technology' pipeline, we anticipate that additional CAR-T cell products will accomplish their 'breakthrough' and clinical proof-of-concept in other indications in hematology and in oncology. Technologies to enhance therapeutic index and facilitate manufacturing will be key for assuring availability and accessibility of CAR-T cell products and their implementation into routine clinical practice.