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

12
Principles and Strategies Employing Heat Shock Proteins
for Immunotherapy of Cancers
Zihai Li
12.1
The Thesis
Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCHVerlag GmbH& Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
Fueled by the idea of immunosurveillance [1] and the dream that tumors can be dealt
with by vaccinations, tumor immunologists have contributed significantly to the development
of immunology, such as in the discovery of major histocompatibility complex
(MHC) molecules, certain cell types like natural killer (NK) cells and cytokines,
including tumor necrosis factor (TNF), and the development of monoclonal antibody
technologies [2]. The immunological properties of heat shock proteins (HSPs) began
to emerge in the 1980s when it was found that HSPs purified from tumor cells can
immunize animals against tumor challenge, despite the fact that there are no tumor-specific
structural changes of HSPs themselves [3]!
HSPs are a family of extremely conserved (from single-celled organisms to Homo sapiens)
ªhousekeepingº molecules that have everything to do with protein folding and
unfolding in the cell [4, 5]. They are subclassified customarily according to their molecular
weight (kDa), such as the family of HSP90, HSP70, HSP60, and low and
high molecular weight HSPs. There are multiple members in each family. For example,
the HSP90 family encompasses cytosolic HSP90a, HSP90b and the endoplasmic
reticular counterpart of HSP90, gp96 or grp94 [6]. On the one hand, HSPs are
detergent-like molecules inside of the cell to prevent millions of millions of proteins
and their intermediates from sticking to one another [7]. On the other hand, the
roles of HSPs in the prevention of protein denaturation and apoptosis explain why
they are often induced by heat (hence the name HSP), or other conditions that lead
to protein unfolding or misfolding [8].
Over the last two decades, several immunological principles of HSPs have been uncovered
(Fig. 12.1). It is now clear that HSPs play broader roles in both innate and
adaptive immunity [3, 9].
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