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


METHODS
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.


RESULTS
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.


CONCLUSIONS
CD40 ligation of APCs in vitro results in the generation of T cells with enhanced effector function against established pulmonary tumors in vivo.


CONCLUSIONS
These findings have direct implications in the development of effective T cell-based immunotherapy of malignant conditions in human beings.
Bergstrom
Richard T
RT
Department of Otolaryngology, Cleveland Clinic Foundation, Ohio 44195, USA.
Silverman
Damon A
DA
Chambers
Kathleen
K
Kim
Julian A
JA
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007371:Interferon-gamma