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Clinical and Developmental Immunology
Volume 2010, Article ID 423781, 12 pages
http://dx.doi.org/10.1155/2010/423781
Review Article

Tumor Antigen-Dependent and Tumor Antigen-Independent Activation of Antitumor Activity in T Cells by a Bispecific Antibody-Modified Tumor Vaccine

1German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
2Tumor Immunology Program, DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
3Medical Centre for Immunology and Oncology (IOZK), 50674 Cologne, Germany

Received 1 July 2010; Accepted 14 December 2010

Academic Editor: Stuart Mannering

Copyright © 2010 Philippe Fournier and Volker Schirrmacher. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

New approaches of therapeutic cancer vaccination are needed to improve the antitumor activity of T cells from cancer patients. We studied over the last years the activation of human T cells for tumor attack. To this end, we combined the personalized therapeutic tumor vaccine ATV-NDV—which is obtained by isolation, short in vitro culture, irradiation, and infection of patient's tumor cells by Newcastle Disease Virus (NDV)—with bispecific antibodies (bsAbs) binding to this vaccine and introducing anti-CD3 (signal 1) and anti-CD28 (signal 2) antibody activities. This vaccine called ATV-NDV/bsAb showed the unique ability to reactivate a preexisting potentially anergized antitumor memory T cell repertoire. But it also activated naive T cells to have antitumor properties in vitro and in vivo. This innovative concept of direct activation of cancer patients' T cells via cognate and noncognate interactions provides potential for inducing strong antitumor activities aiming at overriding T cell anergy and tumor immune escape mechanisms.