Cancer vaccines, a critical review--Part I

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.