Novel strategies for inhibiting PD-1 pathway-mediated immune suppression while simultaneously delivering activating signals to tumor-reactive T cells

Cancer Immunology, Immunotherapy : CII
Suzanne Ostrand-RosenbergJuan A Alvarez

Abstract

We previously developed cell-based vaccines as therapeutics for metastatic cancers. The vaccines were aimed at activating type I CD4(+)T cells and consisted of tumor cells transfected with genes encoding syngeneic MHC class II and CD80 costimulatory molecules, and lacking the MHC II-associated invariant chain. The vaccines showed some efficacy in mice with sarcoma, melanoma, and breast cancer and activated MHC class II syngeneic T cells from breast, lung, and melanoma patients. During the course of the vaccine studies, we observed that CD80 not only costimulated naïve T cells, but also bound to PD-L1 and prevented tumor cell-expressed PD-L1 from binding to its receptor PD-1 on activated T cells. A soluble form of CD80 (CD80-Fc) had the same effect and sustained IFNγ production by both human and murine PD-1(+) activated T cells in the presence of PD-L1(+) human or mouse tumor cells, respectively. In vitro studies with human tumor cells indicated that CD80-Fc was more effective than antibodies to either PD-1 or PD-L1 in sustaining T cell production of IFNγ. Additionally, in vivo studies with a murine tumor demonstrated that CD80-Fc was more effective than antibodies to PD-L1 in extending survival time. Studies with human T cells ...Continue Reading

References

Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·T D ArmstrongS Ostrand-Rosenberg
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshiko IwaiNagahiro Minato
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julia A BrownGordon J Freeman
Apr 22, 2003·Nature Medicine·Tyler J CurielWeiping Zou
May 4, 2004·Nature Reviews. Immunology·Lieping Chen
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yvette E LatchmanArlene H Sharpe
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian P DolanSuzanne Ostrand-Rosenberg
Feb 17, 2006·International Journal of Cancer. Journal International Du Cancer·Christian BlankAndreas Mackensen
Aug 16, 2006·The New England Journal of Medicine·Ganesh SuntharalingamNicki Panoskaltsis
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian P DolanSuzanne Ostrand-Rosenberg
Jan 29, 2008·Blood·Takeshi AzumaLieping Chen
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·David Yin-Wei LinDavid N Garboczi
Jul 1, 2008·Molecular Immunology·Manish J ButteArlene H Sharpe
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael A CurranJames P Allison
Mar 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shari Pilon-ThomasJames J Mulé
Jun 3, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie R BrahmerSuzanne L Topalian
Sep 8, 2010·The Journal of Experimental Medicine·Kaori SakuishiAna C Anderson
May 11, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samuel T HaileSuzanne Ostrand-Rosenberg
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Jun 5, 2012·The New England Journal of Medicine·Julie R BrahmerJon M Wigginton
Jan 29, 2013·Cancer Immunology, Immunotherapy : CII·Martin J CannonMaurizio Chiriva-Internati
Jun 4, 2013·The New England Journal of Medicine·Omid HamidAntoni Ribas
Jun 4, 2013·The New England Journal of Medicine·Jedd D WolchokMario Sznol
Aug 3, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Caroline RobertAlexander M M Eggermont
Aug 7, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samuel T HaileSuzanne Ostrand-Rosenberg
Oct 23, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeffrey S WeberY Ann Chen
Dec 21, 2013·Science·Jennifer Couzin-Frankel
Jan 3, 2014·The Journal of Clinical Investigation·Liufu DengYang-Xin Fu
Jun 5, 2014·Cancer Immunology, Immunotherapy : CII·Rachel M GibbonsHaidong Dong

❮ Previous
Next ❯

Citations

Jan 5, 2016·Cancer Immunology, Immunotherapy : CII·Shamaila Munir AhmadMads Hald Andersen
Nov 30, 2018·Journal for Immunotherapy of Cancer·Daqian GuXiang Xu
Nov 11, 2017·Cancer Immunology Research·Lucas A HornSuzanne Ostrand-Rosenberg
Apr 1, 2021·Medical Oncology·Tatiana Cunha PereiraGabriela Sousa

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.