Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization

Barbon, Christine M.; Yang, Min; Wands, Gregory D.; Ramesh, Radha; Slusher, Barbara S.; Hedley, Mary Lynne; Luby, Thomas M.

doi:10.1016/j.cellimm.2010.02.007

Cited by 36T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization

Barbon, Christine M., Yang, Min, Wands, Gregory D., Ramesh, Radha, Slusher, Barbara S., Hedley, Mary Lynne, Luby, Thomas M.·2010·Cellular Immunology

DOI 10.1016/j.cellimm.2010.02.007

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Abstract

Cyclophosphamide in combination with immunotherapeutic approaches preferentially impinges on T(reg) activity and allows for robust generation of T cell effectors. Reduced dosages of cyclophosphamide are necessary to restrict its cytotoxic effects to the negative regulatory cell populations while sparing effector lymphocytes. We investigated cyclophosphamide dosing in combination with ZYC300, a PLG-encapsulated plasmid DNA vaccine which encodes the cytochrome P450 family member, CYP1B1, a known human tumor-associated antigen. In mice, three consecutive, low doses of cyclophosphamide comprised a superior regimen in enhancing the magnitude, diversity of epitopes, and avidity to individual epitopes of specific T cell responses when compared to regimens that used either a single low or a single high dose. Consecutive low doses of cyclophosphamide predominantly targeted T(regs) while sparing overall T lymphocyte counts. Thus, we report the synergistic activity of pharmacologic T(reg) depletion with cyclophosphamide on quantitatively and qualitatively increasing T cell responses to a known human tumor-associated antigen.

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Low-dose cyclophosphamide depleted circulating and tumor-infiltrating regulatory T cells (Tregs).
“Low-dose cyclophosphamide depleted circulating and tumor-infiltrating regulatory T cells (Tregs) [38–40].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [38]

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Authors: Barbon, C. M., Yang, M., Wands, G. D., Ramesh, R., Slusher, B. S., Hedley, M. L., & Luby, T. M.
Affiliations: Dana-Farber Cancer Institute (US)
Eisai (United States) (US)
Corresponding author: Barbon, Christine M.
ORCID: Yang, Min
Slusher, Barbara S.
Venue: Cellular Immunology
Publisher: Elsevier BV
Published: 2010
Volume: 262
Issue: 2
Pages: 150-161
ISSN: 0008-8749 (ISSN-L)
DOI: 10.1016/j.cellimm.2010.02.007
OpenAlex: W2080716410
Cited by: 36
References: 75
Citations by year: 2024: 3 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 3
FWCI: 1.10
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Cellular Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: cyclophosphamide, regulatory T cells, Treg depletion, low-dose chemotherapy, DNA vaccine, CYP1B1, tumor-associated antigens, T cell response, epitope breadth, epitope avidity, immunotherapy
MeSH terms: Animals, Epitopes, Antigens, Neoplasm, Aryl Hydrocarbon Hydroxylases, Cell Line, Cyclophosphamide, Drug Compounding, Female, Humans, Immunization, Immunosuppressive Agents, Mice, Inbred C3H, Spleen, T-Lymphocyte Subsets, Vaccines, DNA, T-Lymphocytes, Regulatory, Mice, Cytochrome P-450 CYP1B1

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Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization

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