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Fowler D, Nattress C, Navarrete AS, et al. Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment. Cancers (Basel). 2021;13(23)doi: 10.3390/cancers13236000.
Fowler, D., Nattress, C., Navarrete, A. S., Barisa, M., & Fisher, J. (2021). Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment. Cancers, 13(23), . https://doi.org/10.3390/cancers13236000
Fowler, Daniel, et al. "Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment." Cancers vol. 13,23 (2021). doi: https://doi.org/10.3390/cancers13236000
Fowler D, Nattress C, Navarrete AS, Barisa M, Fisher J. Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment. Cancers (Basel). 2021 Nov 29;13(23). doi: 10.3390/cancers13236000. PMID: 34885108; PMCID: PMC8657158.
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Cancers (Basel). 2021 Nov 29;13(23). doi: 10.3390/cancers13236000.

Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment.

Cancers

Daniel Fowler, Callum Nattress, Alba Southern Navarrete, Marta Barisa, Jonathan Fisher

Affiliations

  1. UCL Great Ormond Street Institute of Child Health, 20 Guilford St, London WC1N 1DZ, UK.

PMID: 34885108 PMCID: PMC8657158 DOI: 10.3390/cancers13236000

Abstract

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 vessels for payload delivery into the tumour microenvironment, how these cells are better adapted to overcome the challenges faced in a solid tumour, and importantly, the novel gene engineering approaches required to deliver these more complex polycistronic gene constructs.

Keywords: CAR T cell; armoured CAR T cell; cancer; cell therapy; engineered immune cells; immunosuppression; immunotherapy; payload delivery; solid tumours; tumour microenvironment

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