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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2013-2019.
Prepublished online as a Blood First Edition Paper on June 20, 2007; DOI 10.1182/blood-2006-12-061309.
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Submitted December 4, 2006
Accepted June 19, 2007
An NKT-mediated autologous vaccine generates CD4 T cell-dependent potent anti-lymphoma immunity
Yeonseok Chung, Hong Qin, Chang-Yuil Kang, Sanghee Kim, Larry W. Kwak, and Chen Dong*
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, United States
College of Pharmacy, Seoul National University, Seoul, Korea, Republic of
Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, United States
* Corresponding author; email: cdong{at}mdanderson.org.
Relapses occurring in most lymphoma patients after antibody or chemotherapy highlight a need for effective vaccination approaches. Autologous tumors are ideal sources of patient-specific tumor antigens for vaccines; however, their poor immunogenicity has been a major obstacle in practice. Natural killer T cells (NKT) have recently emerged as crucial regulators of autoimmunity and tumor immunosurveillance. Here, we show that an autologous lymphoma vaccine that activates NKT cells generated tumor-specific protective immunity in experimental mice. Single vaccination with alpha-galactosylceramide ( GC)-loaded A20 lymphoma cells elicited effective anti-tumor immunity against tumor challenge. This vaccination strategy also induced significant tumor regression in A20-bearing mice. Importantly, the survivors from primary tumor inoculation were all resistant to tumor re-challenge, indicative of established adaptive memory immunity. Depletion as well as adoptive transfer studies revealed an exclusive role of conventional CD4+ but not CD8+ T cells in mediating anti-tumor immunity. In addition, we found normal hematopoietic compartments in the vaccinated mice. Therefore, NKT ligand-loaded lymphoma elicits long-lasting and effective anti-tumor immunity, which can be further developed as patient- and tumor-specific immunotherapy against human lymphomas.
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