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In Vivo Sensitized and In Vitro Activated B Cells Mediate Tumor Regression in Cancer Adoptive Immunotherapy¹

Division of Surgical Oncology, University of Michigan, Ann Arbor, MI 48109

Adoptive cellular immunotherapy utilizing tumor-reactive T cells has proven to be a promising strategy for cancer treatment. However, we hypothesize that successful treatment strategies will have to appropriately stimulate not only cellular immunity, but also humoral immunity. We previously reported that B cells in tumor-draining lymph nodes (TDLNs) may function as APCs. In this study, we identified TDLN B cells as effector cells in an adoptive immunotherapy model. In vivo primed and in vitro activated TDLN B cells alone mediated effective (p < 0.05) tumor regression after adoptive transfer into two histologically distinct murine pulmonary metastatic tumor models. Prior lymphodepletion of the host with either chemotherapy or whole-body irradiation augmented the therapeutic efficacy of the adoptively transferred TDLN B cells in the treatment of s.c. tumors as well as metastatic pulmonary tumors. Furthermore, B cell plus T cell transfers resulted in substantially more efficient antitumor responses than B cells or T cells alone (p < 0.05). Activated TDLN B cells conferred strong humoral responses to tumor. This was evident by the production of IgM, IgG, and IgG2b, which bound specifically to tumor cells and led to specific tumor cell lysis in the presence of complement. Collectively, these data indicate that in vivo primed and in vitro activated B cells can be employed as effector cells for cancer therapy. The synergistic antitumor efficacy of cotransferred activated B effector cells and T effector cells represents a novel approach for cancer adoptive immunotherapy.

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 in part by National Institutes of Health Grant CA82529 and by the Gillson Longenbaugh Foundation.

² Address correspondence and reprint requests to Dr. Alfred E. Chang and Dr. Qiao Li, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, 3303 CC, Ann Arbor, MI 48109. E-mail addresses: aechang{at}umich.edu and qiaoli{at}umich.edu

³ Abbreviations used in this paper: TDLN, tumor-draining lymph node; CM, complete medium; TBI, total body irradiation.