Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

230 Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
11
Hybrid Cell Vaccination for Cancer Immune Therapy
Peter Walden, Gernot Stuhler and Uwe Trefzer
11.1
Introduction
Cases of spontaneous regressions of tumors reported for a variety of cancers have
long been interpreted as the result of tumor-specific immune reactions [1]. Burnet
had forged these observations from clinical cases together with the results of pathological
studies and a number of animal model experiments into the concept of immune
surveillance of cancer, and thereby summed up about a century of tumor immunology
[2±4]. Regression zones occasionally observed in melanoma lesions are
frequently referred to as illustrations of cellular immune reactions against the tumor
and correlated with a better prognosis [5, 6]. Such clinical observation together with
an increasing number of reports that demonstrate greatly expanded frequencies of
tumor-specific T cells in cancer patients [7±28] are indicative of active antitumor immune
responses. For several tumor-associated antigens (TAAs), expanded frequencies
of specific T cells have even been demonstrated in healthy individuals [29]. However,
regression areas in melanoma are often seen together with simultaneous tumor
progression at the border zones of the same tumor and, at later stages of the disease,
increasing immune dysfunctions are described in many patients which gradually
eliminate effective specific antitumor immune responses. All these observations suggest
an ongoing struggle of the tumor and the immune system, with tumor progression
being the result of a shift in favor of the tumor and tumor regression a shift in
favor of the immune system. Vaccination for cancer immune therapy thus seems to
aim at a specific modulation of the quality and quantity of this balance, and, maybe,
induction of new antitumor cytotoxic cellular immune responses. Currently, vaccination
in cancer is primarily a therapeutic intervention in contrast to the situation in
the case of infectious diseases. Preventive vaccination against cancer is not yet possible
in humans, but might be attempted in future in specific high-risk situations.
Prerequisite of an active role of adaptive immune responses against cancer is a specific
antigenicity of the tumor cells. The development of specific vaccination strategies
for cancer immune therapy depends on TAAs, but also on the identification of the effector
mechanism used by the immune system. Burnet et al. had suggested already
some 30 years ago that T lymphocytes are the solely most important effector cells in