PMID- 11727535 OWN - NLM STAT- MEDLINE DCOM- 20011217 LR - 20191025 IS - 1471-2598 (Print) IS - 1471-2598 (Linking) VI - 1 IP - 2 DP - 2001 Mar TI - T-cell-directed cancer vaccines: the melanoma model. PG - 277-90 AB - Significant advances in the understanding of the molecular basis for tumour/host interactions in humans have occurred in the last decade through studying patients with metastatic melanoma. This disease is characterised by its tendency to be modulated by immunologic factors. Furthermore, immunologic manipulation of the host with various systemic agents, in particular IL-2, frequently affects this natural phenomenon and can lead to complete rejection of cancer. By studying the cellular immunology occurring in patients undergoing immunotherapy, several tumour antigens (TA) and their epitopes recognised by human leukocyte antigen (HLA) class I-restricted cytotoxic T-lymphocytes (CTL) have been identified. Most of these TA are non-mutated molecules expressed by the majority of melanoma in vivo and most melanoma cell lines. In addition, unique minimal epitopic sequences play an immunodominant role in the context of specific HLA class I alleles. Since melanoma lesions from different patients often share expression of the same TA, and a minimal peptide sequence from a TA can cause immunologic changes in multiple patients, interest has grown in the development of TA-specific vaccines suitable for broad patient populations. Repeated in vitro stimulation of peripheral blood mononuclear cells (PBMC) with TA-derived epitopes can induce a high frequency of TA-reactive T-cells in melanoma patients. The same epitopes can also enhance TA-specific T-cell reactivity in vivo when administered subcutaneously in combination with Incomplete Freund's Adjuvant (IFA). Epitope-based vaccinations, however, have not shown strong clinical efficacy unless combined with IL-2 administration. Attempts to increase the efficacy of these vaccines have combined specialised antigen-presenting cells or the administration of whole TA through DNA- or RNA-based vaccines with the intention of increasing antigen presentation and processing. Save for scattered reports, however, the success of these approaches has been limited and T-cell-directed vaccination against cancer remains at a paradoxical standstill whereby anticancer immunisation can be induced but it is not sufficient, in most cases, to induce tumour regression. Using melanoma as the standard model for immunotherapy, we will review various methods of T-cell-directed vaccination, the monitoring and analysis of the resulting immune response, and several clinical trials in which cancer vaccines have successfully induced immunisation. FAU - Wang, E AU - Wang E AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA. FAU - Phan, G Q AU - Phan GQ FAU - Marincola, F M AU - Marincola FM LA - eng PT - Journal Article PT - Review PL - England TA - Expert Opin Biol Ther JT - Expert opinion on biological therapy JID - 101125414 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (Histocompatibility Antigens) RN - 0 (Peptides) SB - IM MH - Antigens, Neoplasm/immunology MH - Cancer Vaccines/*immunology/therapeutic use MH - Cytokines/analysis/metabolism MH - Dendritic Cells/immunology MH - Gene Expression Regulation MH - Histocompatibility Antigens/immunology MH - Humans MH - Melanoma/*immunology/*therapy MH - Monitoring, Immunologic/methods MH - Peptides/immunology/therapeutic use MH - T-Lymphocytes/*immunology/metabolism RF - 106 EDAT- 2001/12/01 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/12/01 10:00 PHST- 2001/12/01 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/12/01 10:00 [entrez] AID - 10.1517/14712598.1.2.277 [doi] PST - ppublish SO - Expert Opin Biol Ther. 2001 Mar;1(2):277-90. doi: 10.1517/14712598.1.2.277.