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

26 2 Serological Determinants On Tumor Cells
by such vaccines would be a negligible quantity compared to the majority of immune
responses (or tolerance) induced to normal autoantigens by such a vaccine.
The main goal of cancer vaccination is the induction of an effective specific catalytic
response against tumor cells which spares the cells of normal tissues. With respect
to specificity several classes of antigens may be suitable targets; in addition to the
CT antigens, these include differentiation antigens, tumor-associated overexpressed
gene products, mutated gene products and tumor-specific splice variants. Clinically
the most interesting class of antigens is that of the shared tumor antigens or cancertestis
antigens. To cope with the rapidly growing number of CT antigens, a new nomenclature
has been suggested for them [29]. According to the order of their initial
identification the individual genes are designated by enumeration. Since individual
CT antigens are expressed only in a variable proportion of tumors, only the availability
of several CTA could significantly enlarge the proportion of patients eligible for
vaccination studies. In this regard it is interesting that members of a given gene family
tend to be expressed in a co-regulated fashion whereas different gene families
are preferentially expressed in other sets of tumors. It is therefore reasonable to
choose antigens from different CT families to cover as many tumors as possible. Despite
the fact that SEREX enlarged the pool of available tumor antigens, the proportion
of tumors for which no tumor antigen is known is still high, particularly in frequent
neoplasms such as colon and prostate cancer. Moreover, immunohistological
investigations for MAGE antigens have demonstrated a heterogeneity of antigen expression
even in the same tumor specimen [30, 31]. Thus, the use of a mixture of
several antigens to vaccinate in a patient would have the potential of reducing or
even preventing the in vivo selection of antigen-negative clones and would also address
the problem of a heterogeneous expression of a given antigen in an individual
tumor specimen.
For the development of molecular vaccine strategies, the knowledge of antigen-derived
peptide epitopes which are capable of priming or activating specific CTL or T
helper cells is an indispensable prerequisite. Because of the diversity of peptides presented
by the highly polymorphic HLA alleles, the definition of these epitopes by ªreverse
T cell immunologyº represents an enormous challenge. However, we and
others have demonstrated that by using straight-forward strategies, the identification
of epitopes from SEREX-defined antigens which bind and activate either CD8 + or
CD4 + is feasible and has been successful for each SEREX antigen for which the definition
of such epitopes has been pursued.
2.11
Conclusions and Perspectives
The knowledge and availability of a large number of human tumor antigens and
their MHC-binding epitopes has opened the perspective for the development of polyvalent
vaccines for a wide spectrum of human cancers using pure preparations of
antigenic proteins or peptide fragments. Moreover, the study and long-term followup
of large numbers of patients will help to determine the diagnostic and prognostic