Cancer vaccines have been explored clinically against
melanomas,
adenocarcinomas and
lymphomas.
Breast cancer vaccines include
Theratope,
MUC1 mucin peptides and HER-2/neu
peptide vaccines. Phase II trials suggest prolongation of survival of advanced
breast cancer patients who generate high titers of antibody to
Theratope. In contrast,
melanoma ganglioside vaccines, which also elicit only
antibodies, have not been effective in improving survival in controlled trials. Anti-idiotype
vaccines for solid
tumors, which depend upon mimicry of the
tumor-associated
antigens, have also had limited success. In
lymphomas, where the idiotypes are the
tumor-associated
antigens, greater success has been achieved. A number of
tumor-associated
antigens have been identified in
melanoma, such as the lineage related
cancer-testis group (MAGE) and
tyrosinase-related
antigens. Non-lineage related
antigens shared among a variety of very different
tumors have recently been demonstrated too, which may permit immunization against more than one
tumor group.
Telomerase and MG50, one of several
interleukin-1 receptor antagonist molecules, are both immunogenic and widespread in their representation.
Carcinoembryonic antigen is the basis for
vaccines against many
adenocarcinomas. Both viral and non-viral vectors are being used to improve the reactivity to
peptides in
adenocarcinomas. Dendritic cell-carried
vaccines, which package the
antigens ex vivo rather than depending upon in vivo uptake, are being extensively explored in clinical models to improve the effectiveness of defined
vaccines, such as
peptides and
RNA. '
Naked' DNA vaccines injected intramuscularly also have their advocates. Among the most recent attempts to improve the immunogenicity of
vaccines is the use of
antigens newly identified by genomic techniques and 'superagonist'
peptide mimics, selected from combinatorial
peptide libraries. These modern biochemical and molecular
biological methods may greatly expand our ability to immunize against
tumor antigens, which are essentially 'self' molecules. Finally, a greater understanding of ways in which
tumors escape immunological detection or thwart immunological responses should lead to improved strategies against the
tumor to augment the effect of vaccination.