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* Swim Across America Laboratory of Tumor Immunology,
Department of Medicine,
Department of Immunology,
Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and
¶ Weill Graduate School Medical Sciences, Cornell University, New York, NY 10021
Malignant relapse remains a major problem for recipients of allogeneic hemopoietic stem cell transplantation (HSCT). We hypothesized that immunization of allogeneic HSCT recipients against tissue-restricted Ags using DNA vaccines would decrease the risk of relapse without enhancing graft-vs-host disease (GVHD). Using the mouse B16 melanoma model, we found that post-HSCT DNA immunization against a single tumor Ag induces tumor rejection that is significantly greater than HSCT alone in a T cell-depleted MHC-matched minor Ag-mismatched allogeneic HSCT model (LP 
B6). In treatment models, post-HSCT DNA immunization provides significantly greater overall survival than the vaccine alone. Donor leukocyte infusion further enhances tumor-free survival, including in treatment models. There was no GVHD in HSCT recipients treated with DNA vaccination and donor leukocyte infusion. Further analysis demonstrated that these effects are dependent on CD8+ T cells of donor origin that recognize multiple epitopes. These results demonstrate that DNA immunization against tissue-restricted Ags after allogeneic T cell-depleted HSCT can induce potent antitumor effects without causing GVHD.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants CA33049 (to M.-A.P., M.v.B., and A.N.H.), K08-CA10260 (to M.-A.P.), HL69929, HL72412, and CA107096 (to M.v.B.), CA59350, CA58621, CA33049, and CA47179 (to A.N.H.), T32-CA009512 (to A.D.C.), P20-CA103694 (to O.A.) by the National Institutes of Health, by Swim Across America (to M.-A.P., A.D., A.D.C., D.W.H., J.A.G.-P., M.E.E., J.D.W., and A.N.H.), the Byrne Fund from the Memorial Sloan-Kettering Cancer Center (to M.-A.P.), an American Society of Clinical Oncology Young Investigator Award (to A.D.C.), the Clinical Scholars Biomedical Research Training Program and the Charles A. Dana Foundation (to A.D.C.), the Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Cancer Foundation for Research and the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center (to A.N.H., J.A.G.-P., M.E.E., and M.v.B.), by awards from the Emerald Foundation, the Leukemia and Lymphoma Society, and the Golfers against Cancer (to M.v.B.), a Damon Runyon-Lilly Clinical Investigator Award (to J.D.W.), a Fellowship award from the Cancer Research Institute (to M.E.E.), an Amy Strelzer Manasevit Scholar Award from The National Marrow Donor Program and The Marrow Foundation (to O.A.), and the Deutscher Akademischer Austausch Dienst and Boehringer Ingelheim Fonds (to T.H.T.). A.N.H. has Damon Runyon/Eli Lilly mentorship support.
2 M.-A. P. and A. D. contributed equally to this work.
3 Current address: Section of General Surgery, University of Chicago, Mail Code 7114, 5841 South Maryland Avenue, Chicago, IL 60637.
4 Abbreviations used in this paper: HSCT, hemopoietic stem cell transplantation; DLI, donor leukocyte infusion; GVHD, graft-vs-host disease; TRP, tyrosinase-related protein.
5 Address correspondence and reprint requests to Dr. Miguel-Angel Perales, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 298, New York, NY 10021. E-mail address: peralesm{at}mskcc.org
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