Potentiating immune checkpoint blockade therapeutic efficacy using a small molecule activator of integrin cell adhesion receptors

Author & Article Information

  • Authors: Yared Hailemichael; Peter Vanderslice; Robert V. Market; Ronald J. Biediger; Darren G. Woodside; Upendra K. Marathi; Willem W. Overwijk

  • Online ISSN: 1538-7445

  • Print ISSN: 0008-5472

  • ©2019 American Association for Cancer Research.

Source | Cancer Res (2019) 79 (13_Supplement): 5010. https://doi.org/10.1158/1538-7445.AM2019-5010


Abstract

Immune checkpoint blockade (ICB) has therapeutic benefit in several human cancers, but in many patients, ICB - induced T cells do not infiltrate tumors, preventing clinical benefit. Intratumoral T cell accumulation requires firm adhesion mediated by the integrins very late antigen-4 (VLA-4) and lymphocyte function-associated antigen-1 (LFA-1) on activated T cells. The integrin class of cell adhesion receptors also play critical roles in multiple phases of tumor immune responses. Blocking the LFA-1 interaction with its ligand Intercellular adhesion molecule 1 (ICAM-1) abrogates CD8+ tumor infiltration after anti-CTLA4 therapy. Here, we evaluated the effect of an integrin activator, 7HP349, on promoting intratumoral T cell accumulation to potentiate CTLA-4 and PD-L1 checkpoint blockade anti-tumor activity.


See the original article here | American Association for Cancer Research

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Integrin-mediated augmentation of antigenic immunity

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Cell adhesion molecules and their roles and regulation in the immune and tumor microenvironment