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Abstract

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.

STUDY DESIGN: 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.

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

SIGNIFICANCE: These findings have direct implications in the development of effective T cell-based immunotherapy of malignant conditions in human beings.

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CD40 Monoclonal Antibody Activation of Antigen-Presenting Cells Improves Therapeutic Efficacy of Tumor-Specific T Cells

Abstract

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