CD40 monoclonal antibody activation of antigen-presenting cells improves therapeutic efficacy of tumor-specific T cells.

Abstract

The goal of this study was to determine whether CD40 ligation of antigen presenting cells (APCs) enhances the anti-tumor effector function of tumor draining lymph node (TDLN) T lymphocytes in an adoptive immunotherapy model. MCA 205 TDLNs were culture activated both in the presence and absence of a stimulatory anti-CD40 monoclonal antibody (mAb) and effector cell phenotype, cytokine secretion in vitro and therapeutic efficacy in vivo were compared. Anti-CD40 mAb induced upregulation of APC cell surface activation markers that promoted generation of T cells that demonstrated an increase in tumor-specific IFN-gamma secretion and a statistically significant reduction in the number of pulmonary tumors (p< 0.01) after adoptive transfer. CD40 ligation of APCs in vitro results in the generation of T cells with enhanced effector function against established pulmonary tumors in vivo. These findings have direct implications in the development of effective T cell-based immunotherapy of malignant conditions in human beings.