Cancers, Vol. 13, Pages 6000: Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

Cancers, Vol. 13, Pages 6000: Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment Cancers doi: 10.3390/cancers13236000 Authors: Daniel Fowler Callum Nattress Alba Southern Navarrete Marta Barisa Jonathan Fisher Although chimeric antigen receptor (CAR) T cells have shown impressive clinical success against haematological malignancies such as B cell lymphoma and acute lymphoblastic leukaemia, their efficacy against non-haematological solid malignancies has been largely disappointing. Solid tumours pose many additional challenges for CAR T cells that have severely blunted their potency, including homing to the sites of disease, survival and persistence within the adverse conditions of the tumour microenvironment, and above all, the highly immunosuppressive nature of the tumour milieu. Gene engineering approaches for generating immune cells capable of overcoming these hurdles remain an unmet therapeutic need and ongoing area of research. Recent advances have involved gene constructs for membrane-bound and/or secretable proteins that provide added effector cell function over and above the benefits of classical CAR-mediated cytotoxicity, rendering immune cells not only as direct cytotoxic effectors against tumours, but also as vessels for payload delivery capable of both modulating the tumour microenvironment and orchestrating innate and adaptive anti-tumour immunity. We discuss here the novel concept of engineered immune cells as vesse...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research