Allogeneic MHC gene transfer enhances an effective antitumor immunity in the early period of autologous hematopoietic stem cell transplantation.

Allogeneic MHC gene transfer enhances an effective antitumor immunity in the early period of autologous hematopoietic stem cell transplantation. Research Abstract Details 

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Allogeneic MHC gene transfer enhances an effective antitumor immunity in the early period of autologous hematopoietic stem cell transplantation. Abstract Text:

Akihiko Kobayashi,Hidehiko Hara,Masaki Ohashi,Takeshi Nishimoto,Kimiko Yoshida,Nobuhiro Ohkohchi,Teruhiko Yoshida,Kazunori Aoki,Akihiko Kobayashi,Hidehiko Hara,Masaki Ohashi,Takeshi Nishimoto,Kimiko Yoshida,Nobuhiro Ohkohchi,Teruhiko Yoshida,Kazunori Aoki,

PURPOSE: In autologous hematopoietic stem cell transplantation (HSCT), lymphopenia-induced homeostatic proliferation of T cells is driven by the recognition of self-antigens, and there is an opportunity to skew the T-cell repertoire during the T-cell recovery by engaging tumor-associated antigens, leading to a break of tolerance against tumors. However, the homeostatic proliferation-driven antitumor responses seem to decline rapidly in association with tumor growth. We hypothesized that a tumor-specific immune response induced by an immune gene therapy could enhance and sustain homeostatic proliferation-induced antitumor immunity. EXPERIMENTAL DESIGN: The antitumor effect of allogeneic MHC (alloMHC) gene transfer was examined at the early phase of the immune reconstitution after syngeneic HSCT. RESULTS: Syngeneic HSCT showed significant tumor growth inhibition of syngeneic colon cancer cells within a period of 30 days; however, the tumor then resumed rapid growth and the survival of the mice was not prolonged. In contrast, when the alloMHC plasmid was intratumorally injected at the early phase after syngeneic HSCT, the established tumors were markedly regressed and the survival of recipient mice was prolonged without significant toxicities, whereas no survival advantage was recognized in recipient mice injected with a control plasmid. This tumor suppression was evident even in the other tumors that were not injected with the alloMHC plasmid. The antitumor response was characterized by the development of tumor-specific T cell- and natural killer cell-mediated cytotoxicities. CONCLUSION: The results suggest the efficacy and safety of integrating intratumoral alloMHC gene transfer with an autologous HSCT for the treatment of solid cancers.

Allogeneic MHC gene transfer enhances an effective antitumor immunity in the early period of autologous hematopoietic stem cell transplantation. Publishing Authors By Initials

A Kobayashi,H Hara,M Ohashi,T Nishimoto,K Yoshida,N Ohkohchi,T Yoshida,K Aoki,A Kobayashi,H Hara,M Ohashi,T Nishimoto,K Yoshida,N Ohkohchi,T Yoshida,K Aoki,

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Allogeneic MHC gene transfer enhances an effective antitumor immunity in the early period of autologous hematopoietic stem cell transplantation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 7469-79

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: Dec

YEAR: 2007

Allogeneic MHC gene transfer enhances an effective antitumor immunity in the early period of autologous hematopoietic stem cell transplantation. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

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AFFILIATION: Authors' Affiliations: Section for Studies on Host-Immune Response and Genetics Division, National Cancer Center Research Institute, Tokyo, Japan; and Department of Surgery, University of Tsukuba, Tsukuba, Japan.

Country: United States

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MEDLINETA: Clin Cancer Res

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