Basic StudiesAgonistic Antibody to CD40 Boosts the Antitumor Activity of Adoptively Transferred T Cells In VivoLiu, Chengwen; Lewis, Carol M.; Lou, Yanyan; Xu, Chunyu; Peng, Weiyi; Yang, Yan; Gelbard, Alexander H.; Lizée, Gregory; Zhou, Dapeng; Overwijk, Willem W.; Hwu, PatrickAuthor Information Department of Melanoma Medical Oncology, The Center for Cancer Immunology Research, MD Anderson Cancer Center, University of Texas, Houston, TX C.L. and C.M.L. contributed equally. Reprints: Patrick Hwu, Department of Melanoma Medical Oncology, Unit 0430, The Center for Cancer Immunology Research, MD Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail: firstname.lastname@example.org). Received August 2, 2011 Accepted January 29, 2012 Journal of Immunotherapy: April 2012 - Volume 35 - Issue 3 - p 276-282 doi: 10.1097/CJI.0b013e31824e7f43 Buy Metrics Abstract CD40, a member of the tumor necrosis factor receptor superfamily, is broadly expressed on antigen-presenting cells and other cells, including fibroblasts and endothelial cells. Binding of CD40 and its natural ligand CD40L (CD154) triggers cytokine secretion, and increased expression of costimulatory molecules is required for T-cell activation and proliferation. However, to our knowledge, the use of agonistic antibodies to CD40 to boost adoptively transferred T cells in vivo has not been investigated. The purpose of this study was to determine whether anti-CD40 monoclonal antibody (mAb) in combination with interleukin (IL)-2 could improve the efficacy of in vitro-activated T cells to enhance antitumor activity. Mice bearing B16 melanoma tumors expressing the gp100 tumor antigen were treated with cultured, activated T cells transgenic for a T-cell receptor specifically recognizing gp100, with or without anti-CD40 mAb. In this model, the combination of anti-CD40 mAb with IL-2 led to expansion of adoptively transferred T cells and induced a more robust antitumor response. Furthermore, the expression of CD40 on bone marrow-derived cells and the presence of CD80/CD86 in the host were required for the expansion of adoptively transferred T cells. The use of neutralizing mAb to IL-12 provided direct evidence that enhanced IL-12 secretion induced by anti-CD40 mAb was crucial for the expansion of adoptively transferred T cells. Collectively, these findings provide a rationale to evaluate the potential application of anti-CD40 mAb in adoptive T-cell therapy for cancer. © 2012 Lippincott Williams & Wilkins, Inc.