Cancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy

The Journal of Clinical Investigation
Yared HailemichaelWillem W Overwijk

Abstract

Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control. The inflamed vaccination site subsequently also sequestered and destroyed anti-CTLA-4-induced Teffs with specificities for tumor antigens other than gp100, reducing the antitumor efficacy of anti-CTLA-4 therapy. Mechanistically, Teffs at the vaccination site recruited inflammatory monocytes, which in turn attracted additional Teffs in a vicious cycle mediated by IFN-γ, CXCR3, ICAM-1, and CCL2, dependent on IFA formulation. In contrast, nonpersistent vaccine formulations based on dendritic cells, viral vectors, or water-soluble peptides potently synergized with checkpoint blockade of b...Continue Reading

References

Oct 6, 2000·The New England Journal of Medicine·U H von Andrian, C R Mackay
Aug 20, 2003·The Journal of Experimental Medicine·Willem W OverwijkNicholas P Restifo
Jan 1, 2004·The Journal of Clinical Investigation·Kristina SomersaloMichael L Dustin
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vladimir MichailowskyJoão S Silva
May 5, 2007·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Xisheng WangYasuhiro Suzuki
Aug 25, 2007·Nature Reviews. Immunology·Klaus LeySussan Nourshargh
Jul 25, 2008·Nature·Alberto MantovaniFrances Balkwill
Sep 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brian A RabinovichPatrick Hwu
Mar 19, 2009·Cancer Research·Helena HarlinThomas F Gajewski
May 16, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Satish L DeshmaneBassel E Sawaya
Nov 6, 2009·The New England Journal of Medicine·Gemma G KenterCornelis J M Melief
Nov 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Deepa RaiVladimir P Badovinac
Dec 24, 2009·Cancer Research·Zvi G FridlenderSteven M Albelda
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 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Aug 24, 2010·Journal of Translational Medicine·Jochen T SchaeferCraig L Slingluff
Sep 8, 2010·The New England Journal of Medicine·Philip W KantoffUNKNOWN IMPACT Study Investigators
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
May 19, 2012·Seminars in Oncology·Bridget P Keenan, Elizabeth M Jaffee
May 29, 2012·Immunity·Albert Zlotnik, Osamu Yoshie
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Jun 4, 2013·The New England Journal of Medicine·Jedd D WolchokMario Sznol
Aug 30, 2013·Science Translational Medicine·Stefani SprangerThomas F Gajewski
Sep 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicholas A ZumwaldeYoji Shimizu
Oct 17, 2013·British Journal of Cancer·D BedognettiF M Marincola
Feb 18, 2014·Nature·Haipeng LiuDarrell J Irvine
Mar 7, 2014·Science Translational Medicine·Dmitriy ZamarinJames P Allison
Apr 30, 2014·Cancer Immunology Research·James L GulleyJeffrey Schlom
Nov 20, 2014·The New England Journal of Medicine·Alexandra SnyderTimothy A Chan
Nov 28, 2014·Nature·Matthew M GubinRobert D Schreiber

❮ Previous
Next ❯

Citations

Dec 24, 2018·Expert Opinion on Investigational Drugs·Bartosz SzostakAndrzej Pawlik
Nov 10, 2018·Anti-cancer Agents in Medicinal Chemistry·Hanjiao QinZhuo Zhang
Dec 7, 2019·Cancer Immunology, Immunotherapy : CII·Nolan A WagesGina R Petroni
Apr 8, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Peter AbdouZhen Gu
Aug 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathalie VigneronRalf M Leonhardt
Apr 13, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Weijun WeiWeibo Cai
Jul 7, 2018·Seminars in Immunopathology·T TranEric Tartour
Nov 27, 2018·Experimental Hematology & Oncology·Ming YiKongming Wu
Dec 14, 2018·Oncoimmunology·Lucillia BezuLorenzo Galluzzi
Oct 17, 2018·Veterinary Sciences·Chris WeirRachel Allavena
Aug 10, 2020·Clinical and Translational Science·Timothy N J Bullock
Oct 23, 2020·Journal of Personalized Medicine·Vincenzo QuagliarielloNicola Maurea
Apr 4, 2021·Cancers·Francisco J Cueto, David Sancho
Mar 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shubhra SinghManisha Singh
Nov 5, 2021·ACS Biomaterials Science & Engineering·Jorieke WeidenMartijn Verdoes

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
FCS
flow cytometry
FACS

Software Mentioned

Living Image
ImageJ

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cancer Vaccines

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

Related Papers

American Journal of Clinical Dermatology
Mario MandalàDaniela Massi
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Michael A PostowJedd D Wolchok
The New England Journal of Medicine
David R Minor
Proceedings of the National Academy of Sciences of the United States of America
Giao Q PhanSteven A Rosenberg
© 2022 Meta ULC. All rights reserved