Open AccessAllogeneic cell therapy from immunized donors with tumor antigen peptide enhances the antitumor effect after cyclophosphamide‐using non‐myeloablative allogeneic hematopoietic cell transplantation
Author(s) -
Hamaguchi Masumitsu,
Eto Masatoshi,
Kamiryo Yoriyuki,
Takeuchi Ario,
Harano Masahiko,
Tatsugami Katsunori,
Teshima Takanori,
Harada Mamoru,
Yoshikai Yasunobu,
Naito Seiji
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.01014.x
Subject(s) - cyclophosphamide , medicine , transplantation , immunology , immunotherapy , cancer research , donor lymphocyte infusion , cytotoxic t cell , hematopoietic stem cell transplantation , chemotherapy , immune system , biology , biochemistry , in vitro
Non‐myeloablative allogeneic stem cell transplantation is an option for the treatment of hematological malignancies as well as solid tumors. We recently proposed a cyclophosphamide‐using non‐myeloablative cell therapy in which donor lymphocytes infusion (DLI) was carried out after tolerance induction to donor cells. In this study, we tested the possibility that the cyclophosphamide‐using cell therapy could be augmented by pre‐immunization of donors before DLI. We initially assessed whether or not the cyclophosphamide‐using cell therapy could also show antitumor effect against subcutaneously established colon 26 carcinoma. As a tumor antigen‐derived peptide for colon 26, we used AH1, an immunodominant H‐2L d ‐binding peptide derived from the envelope protein (gp70) of an endogenous murine leukemia virus. The cyclophosphamide‐using cell therapy with the DLI from donors which were pre‐immunized with the AH1 peptide was compared with that from non‐immunized mice. The cyclophosphamide‐using cell therapy significantly suppressed subcutaneously established colon 26 carcinoma, and the tumor‐rejected mice acquired the tumor‐specific protective immunity. When combined with the DLI from donors that were immunized with AH1, antitumor effect of the cyclophosphamide‐using cell therapy was significantly augmented. The DLI from tumor peptide‐immunized donors showed no influence on donor chimerism and bodyweight of the treated mice, indicating no increased risk of graft‐versus‐host disease. Tumor‐specific cytotoxic T lymphocytes could be generated from tumor‐rejected mice. Our results indicate that the cyclophosphamide‐using non‐myeloablative cell therapy with the DLI from tumor peptide‐immunized donors is a useful protocol to augment graft‐versus‐tumor effect without exacerbation of graft‐versus‐host disease. ( Cancer Sci 2009; 100: 138–143)