The Allogeneic Effect Revisited: Exogenous Help for Endogenous, Tumor-Specific T Cells

Heather J. Symons; Moshe Y. Levy; Jie Wang; Xiaotao Zhou; Gang Zhou; Sarah E. Cohen; Leo Luznik; Hyam I. Levitsky; Ephraim J. Fuchs

doi:10.1016/j.bbmt.2008.02.013

The Allogeneic Effect Revisited: Exogenous Help for Endogenous, Tumor-Specific T Cells

Heather J. Symons, Moshe Y. Levy, Jie Wang, Xiaotao Zhou, Gang Zhou, Sarah E. Cohen, Leo Luznik, Hyam I. Levitsky, Ephraim J. Fuchs

School of Medicine

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

The "allogeneic effect" refers to the induction of host B cell antibody synthesis or host T cell cytotoxicity, including tumoricidal activity, by an infusion of allogeneic lymphocytes. We show that treatment of mice with cyclophosphamide (Cy) followed by CD8⁺ T cell-depleted allogeneic donor lymphocyte infusion (Cy + CD8^- DLI) induces regression of established tumors with minimal toxicity in models of both hematologic and solid cancers, even though the donor cells are eventually rejected by the host immune system. The optimal antitumor effect of Cy + CD8^- DLI required the presence of donor CD4⁺ T cells, host CD8⁺ T cells, and alloantigen expression by normal host but not tumor tissue. The results support a model in which a donor CD4⁺ T cell-mediated graft-versus-host (GVH) reaction effectively awakens antitumor immunity among Cy-resistant host CD8⁺ T cells. These events provide the cellular mechanism of the "allogeneic effect" in antitumor immunity. Cy + CD8^- DLI may be an effective and minimally toxic strategy for awakening the host immune response to advanced cancers.

Original language	English (US)
Pages (from-to)	499-509
Number of pages	11
Journal	Biology of Blood and Marrow Transplantation
Volume	14
Issue number	5
DOIs	https://doi.org/10.1016/j.bbmt.2008.02.013
State	Published - May 2008

Keywords

Adoptive immunotherapy
Allogeneic
Cyclophosphamide
Graft-versus-host disease
Lymphocyte subsets
graft-versus-tumor effects

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2008.02.013

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title = "The Allogeneic Effect Revisited: Exogenous Help for Endogenous, Tumor-Specific T Cells",

abstract = "The {"}allogeneic effect{"} refers to the induction of host B cell antibody synthesis or host T cell cytotoxicity, including tumoricidal activity, by an infusion of allogeneic lymphocytes. We show that treatment of mice with cyclophosphamide (Cy) followed by CD8+ T cell-depleted allogeneic donor lymphocyte infusion (Cy + CD8- DLI) induces regression of established tumors with minimal toxicity in models of both hematologic and solid cancers, even though the donor cells are eventually rejected by the host immune system. The optimal antitumor effect of Cy + CD8- DLI required the presence of donor CD4+ T cells, host CD8+ T cells, and alloantigen expression by normal host but not tumor tissue. The results support a model in which a donor CD4+ T cell-mediated graft-versus-host (GVH) reaction effectively awakens antitumor immunity among Cy-resistant host CD8+ T cells. These events provide the cellular mechanism of the {"}allogeneic effect{"} in antitumor immunity. Cy + CD8- DLI may be an effective and minimally toxic strategy for awakening the host immune response to advanced cancers.",

keywords = "Adoptive immunotherapy, Allogeneic, Cyclophosphamide, Graft-versus-host disease, Lymphocyte subsets, graft-versus-tumor effects",

author = "Symons, {Heather J.} and Levy, {Moshe Y.} and Jie Wang and Xiaotao Zhou and Gang Zhou and Cohen, {Sarah E.} and Leo Luznik and Levitsky, {Hyam I.} and Fuchs, {Ephraim J.}",

note = "Funding Information: We thank Dr. Drew Pardoll for his assistance in reviewing and editing this manuscript. This work was supported by the National Institutes of Health Grants PO1 CA-15396 (Richard J. Jones, M.D., PI) and R01 CA105148 (EJF). E.J.F. is a Leukemia and Lymphoma Society Scholar in Clinical Research. ",

year = "2008",

month = may,

doi = "10.1016/j.bbmt.2008.02.013",

language = "English (US)",

volume = "14",

pages = "499--509",

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TY - JOUR

T1 - The Allogeneic Effect Revisited

T2 - Exogenous Help for Endogenous, Tumor-Specific T Cells

AU - Symons, Heather J.

AU - Levy, Moshe Y.

AU - Wang, Jie

AU - Zhou, Xiaotao

AU - Zhou, Gang

AU - Cohen, Sarah E.

AU - Luznik, Leo

AU - Levitsky, Hyam I.

AU - Fuchs, Ephraim J.

N1 - Funding Information: We thank Dr. Drew Pardoll for his assistance in reviewing and editing this manuscript. This work was supported by the National Institutes of Health Grants PO1 CA-15396 (Richard J. Jones, M.D., PI) and R01 CA105148 (EJF). E.J.F. is a Leukemia and Lymphoma Society Scholar in Clinical Research.

PY - 2008/5

Y1 - 2008/5

N2 - The "allogeneic effect" refers to the induction of host B cell antibody synthesis or host T cell cytotoxicity, including tumoricidal activity, by an infusion of allogeneic lymphocytes. We show that treatment of mice with cyclophosphamide (Cy) followed by CD8+ T cell-depleted allogeneic donor lymphocyte infusion (Cy + CD8- DLI) induces regression of established tumors with minimal toxicity in models of both hematologic and solid cancers, even though the donor cells are eventually rejected by the host immune system. The optimal antitumor effect of Cy + CD8- DLI required the presence of donor CD4+ T cells, host CD8+ T cells, and alloantigen expression by normal host but not tumor tissue. The results support a model in which a donor CD4+ T cell-mediated graft-versus-host (GVH) reaction effectively awakens antitumor immunity among Cy-resistant host CD8+ T cells. These events provide the cellular mechanism of the "allogeneic effect" in antitumor immunity. Cy + CD8- DLI may be an effective and minimally toxic strategy for awakening the host immune response to advanced cancers.

AB - The "allogeneic effect" refers to the induction of host B cell antibody synthesis or host T cell cytotoxicity, including tumoricidal activity, by an infusion of allogeneic lymphocytes. We show that treatment of mice with cyclophosphamide (Cy) followed by CD8+ T cell-depleted allogeneic donor lymphocyte infusion (Cy + CD8- DLI) induces regression of established tumors with minimal toxicity in models of both hematologic and solid cancers, even though the donor cells are eventually rejected by the host immune system. The optimal antitumor effect of Cy + CD8- DLI required the presence of donor CD4+ T cells, host CD8+ T cells, and alloantigen expression by normal host but not tumor tissue. The results support a model in which a donor CD4+ T cell-mediated graft-versus-host (GVH) reaction effectively awakens antitumor immunity among Cy-resistant host CD8+ T cells. These events provide the cellular mechanism of the "allogeneic effect" in antitumor immunity. Cy + CD8- DLI may be an effective and minimally toxic strategy for awakening the host immune response to advanced cancers.

KW - Adoptive immunotherapy

KW - Allogeneic

KW - Cyclophosphamide

KW - Graft-versus-host disease

KW - Lymphocyte subsets

KW - graft-versus-tumor effects

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The Allogeneic Effect Revisited: Exogenous Help for Endogenous, Tumor-Specific T Cells

Abstract

Keywords

ASJC Scopus subject areas

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