An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

Vaccines
Felicity C StarkLakshmi Krishnan

Abstract

Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8⁺ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA) melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8⁺ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8⁺ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8⁺ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8⁺ T cells had an increased expression of programmed cell death protein-1 (PD-1) compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18), sign...Continue Reading

References

Jan 14, 1994·Cell·K A HogquistF R Carbone
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·L KrishnanG D Sprott
May 1, 2001·Immunology·D M BrownE M Lord
Jan 17, 2003·The New England Journal of Medicine·Lin ZhangGeorge Coukos
Jun 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel L BarberRafi Ahmed
Sep 3, 2003·Nature Reviews. Cancer·Mark E Dudley, Steven A Rosenberg
Feb 17, 2006·International Journal of Cancer. Journal International Du Cancer·Christian BlankAndreas Mackensen
Jul 11, 2006·Immunological Reviews·Christopher A KlebanoffNicholas P Restifo
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lakshmi KrishnanG Dennis Sprott
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marsha S RussellSubash Sad
Dec 14, 2007·Cancer Treatment Reviews·Caroline HammUNKNOWN Melanoma Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
Mar 18, 2008·Vaccine·Lakshmi Krishnan, G Dennis Sprott
Mar 24, 2009·Current Opinion in Immunology·Steven A Rosenberg, Mark E Dudley
Jun 9, 2009·Current Opinion in Immunology·Shan Lu
Nov 18, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M BalchVernon K Sondak
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael A CurranJames P Allison
Mar 30, 2010·Cancer Immunology, Immunotherapy : CII·Lisa BorknerChristian Blank
May 28, 2010·Journal of Cutaneous Pathology·F Stephen Hodi, Glenn Dranoff
Oct 16, 2010·Journal of Immunotherapy·Takashi InozumeJames C Yang
Feb 15, 2011·Clinical & Developmental Immunology·Lakshmi KrishnanG Dennis Sprott
Apr 8, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Martin A Cheever, Celestia S Higano
Jul 9, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher A KlebanoffNicholas P Restifo
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jun 4, 2013·The New England Journal of Medicine·Jedd D WolchokMario Sznol
Jan 22, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael A PostowJedd D Wolchok
Apr 4, 2015·Science·Padmanee Sharma, James P Allison
Apr 22, 2015·The New England Journal of Medicine·Michael A PostowF Stephen Hodi
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
Jul 18, 2015·British Journal of Haematology·Karl S Peggs
Jul 25, 2015·Nature Reviews. Cancer·Ignacio MeleroJohn Haanen
Jan 29, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chan-Young OckDae Seog Heo
Feb 7, 2016·BMC Medicine·Jason M RedmanMichael B Atkins
Jun 9, 2016·Expert Review of Vaccines·K HaqL Krishnan
Nov 10, 2016·Vaccines·Soumaya KarakiEric Tartour

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Citations

Nov 26, 2019·Oncotarget·María José Godoy-CalderónAna Federica Convit
Aug 3, 2019·Acta Pharmacologica Sinica·Ang GaoHai-Jun Yu
Mar 13, 2021·Advanced Healthcare Materials·Mengying HeHuabing Chen
Oct 14, 2019·ACS Biomaterials Science & Engineering·Hyemin KimSei Kwang Hahn
Sep 10, 2021·International Journal of Pharmaceutics·Zhiling LiuPeng Zhang

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Methods Mentioned

BETA
flow cytometry
FACS
density gradient centrifugation

Software Mentioned

FACS Diva

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