Cancer vaccines, a critical review--Part II.
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.
Mitchell
Malcolm S
MS
Karmanos Cancer Institute, Detroit, MI 48201, USA. mitchell@karmanos.org
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000494:pharmacology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D005822:Genetic Vectors / Q000494:pharmacology / Q000627:therapeutic use; D006433:Hemocyanins / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; C099077:sialyl-Tn antigen-keyhole-limpet hemocyanin conjugate; D006433:Hemocyanins