Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors

Greta Garrido; Brett Schrand; Agata Levay; Ailem Rabasa; Anthony Ferrantella; Diane M Da Silva; Francesca D'Eramo; Koen A Marijt; Zhuoran Zhang; Deukwoo Kwon; Marcin Kortylewski; W Martin Kast; Vikas Dudeja; Thorbald van Hall; Eli Gilboa

doi:10.1158/2326-6066.CIR-20-0020

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Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors

Journal article

Peer reviewed

Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors

Greta Garrido, Brett Schrand, Agata Levay, Ailem Rabasa, Anthony Ferrantella, Diane M Da Silva, Francesca D'Eramo, Koen A Marijt, Zhuoran Zhang, Deukwoo Kwon, …

Cancer immunology research, Vol.8(7), pp.856-868

07/01/2020

DOI: 10.1158/2326-6066.CIR-20-0020

PMID: 32295785

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Abstract

Vaccination of patients against neoantigens expressed in concurrent tumors, recurrent tumors, or tumors developing in individuals at risk of cancer is posing major challenges in terms of which antigens to target and is limited to patients expressing neoantigens in their tumors. Here, we describe a vaccination strategy against antigens that were induced in tumor cells by downregulation of the peptide transporter associated with antigen processing (TAP). Vaccination against TAP downregulation-induced antigens was more effective than vaccination against mutation-derived neoantigens, was devoid of measurable toxicity, and inhibited the growth of concurrent and future tumors in models of recurrence and premalignant disease. Human CD8 T cells stimulated with TAP dendritic cells elicited a polyclonal T-cell response that recognized tumor cells with experimentally reduced TAP expression. Vaccination against TAP downregulation-induced antigens overcomes the main limitations of vaccinating against mostly unique tumor-resident neoantigens and could represent a simpler vaccination strategy that will be applicable to most patients with cancer.

Animals

Antigen Presentation - immunology

Antigens, Neoplasm - immunology

ATP-Binding Cassette Transporters - antagonists & inhibitors

ATP-Binding Cassette Transporters - immunology

Cancer Vaccines - administration & dosage

Cancer Vaccines - immunology

CD8-Positive T-Lymphocytes - immunology

Cell Line, Tumor

Disease Models, Animal

Female

Humans

Mice

Mice, Inbred BALB C

Mice, Inbred C57BL

Neoplasm Recurrence, Local - immunology

Neoplasm Recurrence, Local - therapy

Neoplasms - immunology

Neoplasms - therapy

RNA, Small Interfering - genetics

Details

Title: Subtitle: Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors
Creators: Greta Garrido - University of Miami
Brett Schrand - University of Miami
Agata Levay - University of Miami
Ailem Rabasa - University of Miami
Anthony Ferrantella - University of Miami
Diane M Da Silva - University of Southern California
Francesca D'Eramo - University of Miami
Koen A Marijt - Leiden University Medical Center
Zhuoran Zhang - City Of Hope National Medical Center
Deukwoo Kwon - University of Miami
Marcin Kortylewski - City Of Hope National Medical Center
W Martin Kast - University of Southern California
Vikas Dudeja - University of Miami
Thorbald van Hall - Leiden University Medical Center
Eli Gilboa - University of Miami
Resource Type: Journal article
Publication Details: Cancer immunology research, Vol.8(7), pp.856-868
DOI: 10.1158/2326-6066.CIR-20-0020
PMID: 32295785
NLM abbreviation: Cancer Immunol Res
ISSN: 2326-6066
eISSN: 2326-6074
Grant note: P30 CA033572 / NCI NIH HHS P30 CA240139 / NCI NIH HHS
Language: English
Date published: 07/01/2020
Academic Unit: Anatomy and Cell Biology; Surgery
Record Identifier: 9985244572702771

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