Cancer vaccines are more properly referred to as 'active specific
immunotherapy', and are used to treat
cancers rather than to prevent them, at least at present.
Vaccines augment already established
tumor immunity, are far more specific against the
tumor than
cytokines, have little or no toxicity, and thus may easily be combined with other types of
immunotherapy. They also elicit immunological memory, which may check recurrence of the
tumor.
Melanoma vaccines have received the most attention thus far. Among the several
vaccines in clinical trials are whole cell lysates, such as
Melacine,
hapten-treated autologous
melanoma cells (M-Vax) and irradiated allogeneic cells (
CancerVax). Regressions of metastatic nodules have been noted with each preparation. Controlled trials of
Melacine indicate prolongation of survival in patients with resected stage IIB disease, particularly those with one or more of the following HLA class I alleles:
HLA-A2 or -A28 (-A6802),
HLA-B12, -44 or -45, and HLA-C3. A combination of
interferon-alpha2b and
Melacine appears to enhance the anti-
tumor response in advanced (stage IV) disease, and is being tested in a large randomized controlled trial in resected stage III disease. An irradiated autologous colon
carcinoma vaccine has improved relapse-free survival in resected stage II disease (Dukes B) in a controlled trial. Second-generation whole cell
vaccines include those incorporating genes such as
GM-CSF or CD80 (B7-1) to improve immunogenicity, and the use of immunogenic cell membranes such as large multivalent immunogen (LMI). Upregulation of HLA class II molecules and concomitant inhibition of the Ii molecule are also being explored as a strategyfor improved presentation of
tumor-associated
antigens in
vaccines. Complex whole cell-derived
vaccines have given clinically superior responses compared to
vaccines containing well-defined
antigens, such as
peptides or
gangliosides; however, well-defined
vaccines are theoretically more desirable because of their reproducibility.