Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading

Gang Xin; Achia Khatun; Paytsar Topchyan; Ryan Zander; Peter J Volberding; Yao Chen; Jian Shen; Chunmei Fu; Aimin Jiang; William A See; Weiguo Cui

doi:10.1158/2326-6066.CIR-19-0251

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Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading

Journal article

Open access

Peer reviewed

Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading

Gang Xin, Achia Khatun, Paytsar Topchyan, Ryan Zander, Peter J Volberding, Yao Chen, Jian Shen, Chunmei Fu, Aimin Jiang, William A See, …

Cancer immunology research, Vol.8(1), pp.7-18

01/2020

DOI: 10.1158/2326-6066.CIR-19-0251

PMCID: PMC6946848

PMID: 31719059

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https://doi.org/10.1158/2326-6066.CIR-19-0251View

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Abstract

Loss of target antigens in tumor cells has become one of the major hurdles limiting the efficacy of adoptive cell therapy (ACT)-based immunotherapies. The optimal approach to overcome this challenge includes broadening the immune response from the initially targeted tumor-associated antigen (TAA) to other TAAs expressed in the tumor. To induce a more broadly targeted antitumor response, we utilized our previously developed Re-energized ACT (ReACT), which capitalizes on the synergistic effect of pathogen-based immunotherapy and ACT. In this study, we showed that ReACT induced a sufficient endogenous CD8 T-cell response beyond the initial target to prevent the outgrowth of antigen loss variants in a B16-F10 melanoma model. Sequentially, selective depletion experiments revealed that Batf3-driven cDC1s were essential for the activation of endogenous tumor-specific CD8 T cells. In ReACT-treated mice that eradicated tumors, we observed that endogenous CD8 T cells differentiated into memory cells and facilitated the rejection of local and distal tumor rechallenge. By targeting one TAA with ReACT, we provided broader TAA coverage to counter antigen escape and generate a durable memory response against local relapse and metastasis. .

Animals

Antigens, Neoplasm - immunology

Antigens, Neoplasm - metabolism

CD8-Positive T-Lymphocytes - immunology

Cell Line, Tumor

Female

gp100 Melanoma Antigen - immunology

Immunologic Memory

Immunotherapy, Adoptive - methods

Listeria monocytogenes - pathogenicity

Listeriosis - complications

Listeriosis - immunology

Listeriosis - microbiology

Melanoma, Experimental - immunology

Melanoma, Experimental - metabolism

Melanoma, Experimental - microbiology

Melanoma, Experimental - therapy

Mice

Mice, Inbred C57BL

Skin Neoplasms - immunology

Skin Neoplasms - metabolism

Skin Neoplasms - microbiology

Skin Neoplasms - therapy

Details

Title: Subtitle: Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading
Creators: Gang Xin - Versiti Blood Center of Wisconsin
Achia Khatun - Versiti Blood Center of Wisconsin
Paytsar Topchyan - Medical College of Wisconsin
Ryan Zander - Versiti Blood Center of Wisconsin
Peter J Volberding - Medical College of Wisconsin
Yao Chen - Versiti Blood Center of Wisconsin
Jian Shen - Versiti Blood Center of Wisconsin
Chunmei Fu - Roswell Park Cancer Institute
Aimin Jiang - Roswell Park Cancer Institute
William A See - Medical College of Wisconsin
Weiguo Cui - Versiti Blood Center of Wisconsin
Resource Type: Journal article
Publication Details: Cancer immunology research, Vol.8(1), pp.7-18
DOI: 10.1158/2326-6066.CIR-19-0251
PMID: 31719059
PMCID: PMC6946848
ISSN: 2326-6066
eISSN: 2326-6074
Grant note: R01 CA198105 / NCI NIH HHS R01 AI125741 / NIAID NIH HHS T32 GM080202 / NIGMS NIH HHS
Language: English
Date published: 01/2020
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297319902771

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