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Chimeric Antigen Receptors for the Tumour Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1263))

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy has dramatically revolutionised cancer treatment. The FDA approval of two CAR-T cell products for otherwise incurable refractory B-cell acute lymphoblastic leukaemia (B-ALL) and aggressive B-cell non-Hodgkin lymphoma has established this treatment as an effective immunotherapy option. The race for extending CAR-T therapy for various tumours is well and truly underway. However, response rates in solid organ cancers have been inadequate thus far, partly due to challenges posed by the tumour microenvironment (TME). The TME is a complex structure whose role is to subserve the persistence and proliferation of tumours as well as support their escape from immune surveillance. It presents several obstacles like inhibitory immune checkpoint proteins, immunosuppressive cells, cytokines, chemokines, stromal factors and adverse metabolic pathways. CAR structure and CAR-T therapies have evolved to overcome these obstacles, and we now have several novel CARs with improved anti-tumour activity demonstrated in xenograft models and in some clinical trials. This chapter provides a discussion of the evolution of CAR-T therapies to enable targeting specific aspects of the TME.

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  1. Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Rosemary Habib, Kenneth Micklethwaite & Kavitha Gowrishankar

  2. Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia

    Rosemary Habib, Adnan Nagrial & Kenneth Micklethwaite

  3. Sydney Cellular Therapies Laboratory, Blood and Bone Marrow Transplant Unit, Department of Haematology, Sydney Medical School, Westmead Hospital, Sydney, NSW, Australia

    Kenneth Micklethwaite

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Habib, R., Nagrial, A., Micklethwaite, K., Gowrishankar, K. (2020). Chimeric Antigen Receptors for the Tumour Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1263. Springer, Cham. https://doi.org/10.1007/978-3-030-44518-8_8

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