Abstract 1938: Superiority of B plus T cell therapy in a spontaneous pulmonary metastasis model
Authors: Xiangming Lao, Qiao Li, Ji Yet, Shengping Li, Alfred E. Chang
Journal: Cancer Research (2010)

Abstract We have previously reported that tumor-draining lymph node (TDLN) B cells can be therapeutic effector cells in cancer adoptive immunotherapy. In vivo primed and in vitro activated TDLN B cells mediated effective tumor regression after adoptive therapy of either experimentally induced pulmonary metastases or sc tumors using two histologically distinct tumor models (B16-D5 and MCA 205 in B6 hosts). 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. In this study, we investigated the ability of treating spontaneous metastases with B effector cells alone and in combination with T cells. To do this, we have used the 4T1 mammary carcinoma that is syngeneic in Balb/c hosts. Inoculating 105 tumor cells into the mammary fat pad results in the development of spontaneous pulmonary metastases that can be enumerated 4 weeks later. T and B cells purified from lymph nodes draining the s.c 4T1 tumor were activated with anti-CD3/anti-CD28 or LPS/anti-CD40, respectively. These cells were adoptively transferred into mice inoculated with 4T1 tumor cells in the fat pads. By week 4, the mice were euthanized and the lung metastases enumerated. Adoptively transferred 4T1 TDLN T cells or B cells each inhibited spontaneous pulmonary metastasis of 4T1 breast cancer cells injected into the mammary fat pads. Activated 4T1 TDLN T cells and 4T1 TDLN B cells used for adoptive transfer produced large amount of cytokine (e.g. IFN-gamma, GM-CSF) and antibody (e.g. IgM, IgG) respectively. We proceeded to treat the spontaneous metastases by T cells plus B cells. Mixed T and B cells purified from the 4T1 TDLN were activated with anti-CD3/anti-CD28+LPS/anti-CD40. While LPS/anti-CD40-activated B cells alone resulted in diminished lung tumors as observed in the previous experiment, the combination of T and B cells resulted in a significantly greater (p&amp;lt;0.05) reduction of lung tumors than that when B cells were transferred alone. T plus B cell-mediated antitumor activity was dose-dependent on the number of T and B cells given. While adoptively transferred B cells produced IgM and IgG, the activated mixture of T+B cells used for adoptive transfer produced both cytokines (e.g. IFN-gamma, GM-CSF) and antibodies (e.g. IgM, IgG). These results support the conclusion that the superior antitumor activity of T+B cells is correlated with the simultaneous modulation of cellular and humoral responses. These findings in a spontaneous pulmonary metastasis model that more closely mimics human cancers may provide alternative strategies in developing more potent adoptive cellular therapies for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1938.