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.
authors.affiliation: Division of Cancer Immunology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Symons
authors.forename: Moshe Y
authors.initials: MY
authors.lastname: Levy
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Cohen
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.forename: Hyam I
authors.initials: HI
authors.lastname: Levitsky
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000627:therapeutic use; D006087:Graft vs Host Reaction / Q000276:immunology*; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide