Journal of Vaccines & Vaccination

Polarized dendritic cells in the immunotherapy of established cancer: Directing effector T Cells to tumors

International Conference & Exhibition on Vaccines & Vaccination

22-24 Nov 2011 Philadelphia Airport Marriott, USA

Pawel Kalinski

Accepted Abstracts: J Vaccines Vaccin

Abstract:

Despite recent evidence that therapeutic can cer vaccines can prolong survival of cancer patients, their eff ectiveness in inducing regression of established tumor lesions remains low. Application of ex-vivo -generated dendritic cells (DCs) as carriers of tumor antigens helps to sidestep the dysfunction of endogenous DCs in cancer patients and allows for controlled delivery of �signal 3� that induces T cell eff ector functions, and �signal 4� that regulates T cell homing. Type-1-polarized DCs (DC1) show strongly enhanced ability to induce tumor-specifi c CTLs and Th 1 cells, when compared with immature or mature nonpolarized DCs. Th ey also preferentially interact with na�ve, central memory, and eff ector T cells, but show reduced activity in attracting undesirable Tregs. DC1s are particularly eff ective in inducing the eff ector pathway of diff erentiation of na�ve and memory T cells and promote T cell expression of CXCR3 and CCR5, the receptors for MIG/CXCL9, IP10/CXCL10 and RANTES/CCL5.While the above chemokines are spontaneously produced by a fraction of tumors, their uniform high expression in all tumor lesions can be induced in a tumor-selective manner by defi ned (tumor-specifi c) combinations of clinically-applicable biologic agents, facilitating tumor entry of the vaccination- induced CTLs. DC1-based vaccines are currently being evaluated in phase I/II clinical trials for patients with malignant glioma, melanoma, colorectal, and prostate cancers, either as single treatments or in combination with tumor-selective chemokine modulation.