A variety of distinct and redundant mechanisms support tumour propagation and survival. Tumour parenchyma consists of a variety of geographically diverse cells with varying genetic expression among subclonal populations. Additionally, the solid tumour microenvironment consists of a dense network of stromal, vascular and immune cells altered by a number of mechanisms not only to tolerate but often to enhance cancer growth. The limited spectrum of chimaeric antigen receptor (CAR) T-cell specificity in the face of this dynamic landscape is one of the greatest challenges facing CAR T-cell therapy for solid tumours. Thus targeting multiple cancer-specific markers simultaneously could result in improved efficacy by broadening the therapeutic reach to include multiple subclonal populations of the tumour parenchyma as well as elements of the tumour microenvironment. Over the last 10 years, we and others have developed multiplex platforms that target the tumour profile rather than single tumour-restricted antigens. These platforms introduce a new dimension that may be key to the successful development of T-cell therapies for solid tumours and to the mitigation of relapses due to antigen escape.
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April 2016
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Cover Image
Endoplasmic reticulumendosome contact sites. This pseudo-colored electron microscopy image shows the formation of inter-organelle membrane contact sites between late endosomes (magenta) and the endoplasmic reticulum (ER; green). This tethering results from the interaction between two ER-anchored proteins (VAP-A and VAP-B) and the late endosomeanchored protein STARD3NL. Mitochondria: brown; nucleus: blue. For further details see pp. 493-498. Image kindly provided by Fabien Alpy. - PDF Icon PDF LinkTable of Contents
Review Article|
April 11 2016
Targeting the tumour profile using broad spectrum chimaeric antigen receptor T-cells
Shoba A. Navai;
Shoba A. Navai
1
*Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Texas Children's Cancer and Hematology Centers, Houston, TX 77030, U.S.A.
‡Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, U.S.A.
§Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, U.S.A.
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Nabil Ahmed
Nabil Ahmed
1
*Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Texas Children's Cancer and Hematology Centers, Houston, TX 77030, U.S.A.
‡Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, U.S.A.
§Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, U.S.A.
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Publisher: Portland Press Ltd
Received:
February 03 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (2): 391–396.
Article history
Received:
February 03 2016
Citation
Shoba A. Navai, Nabil Ahmed; Targeting the tumour profile using broad spectrum chimaeric antigen receptor T-cells. Biochem Soc Trans 15 April 2016; 44 (2): 391–396. doi: https://doi.org/10.1042/BST20150266
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