Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
The prospects for immunotherapy of virus associated cancers (Meeting abstract).
Br J Cancer; 69(Suppl 21):4 1994. Unique Identifier : AIDSLINE ICDB/95611940 Melief CJ; Dept. of Immunohematology and Blood Bank, Univ. Hosp. Leiden,; P.O. Box 9600, 2300 RC Leiden, The Netherlands
Abstract:
Immunotherapy of tumors by adoptive transfer of cytotoxic T cells (CTL) is now feasible in experimental murine systems. These CTL recognize peptide sequences of defined length presented in the groove of MHC class I molecules. Effective eradication of large tumor masses requires co-administration of IL-2. Tumor escape strategies are numerous, but in various instances can be counteracted by defined measures. Initiation of CTL responses against poorly immunogenic non-virus-induced tumors (the majority of human cancer) requires novel strategies to overcome T cell inertia. Rather than wait-and-see whether tumor specific CTL (against unknown antigens) can be cultured from tumor infiltrating lymphocytes we propose an alternative strategy in which CTL are raised against target molecules of choice including differentiation antigens of restricted tissue distribution (autoantigens) or mutated/overexpressed oncogene products. The various steps proposed include (1) identification of target molecules of choice, (2) identification in these target molecules of MHC allele-specific peptide motifs involved in peptide binding to MHC molecules, (3) evaluation of actual binding of such peptides to specific MHC class I molecules, (4) in vitro CTL response induction by such peptides, presented by highly efficient antigen presenting cells such as processing defective cells, carrying empty MHC class I molecules, loaded with a single peptide or dendritic cells. Both types of cells are capable of primary CTL response induction in vitro: (5) Adoptive transfer of tumor specific CTL generated in vitro or, more convenient, vaccination with immunodominant peptides. These various steps have now been taken for several viruses, viral-induced tumors and other types of tumors and the first indications that this strategy is useful have been obtained. A list of potential target molecules for T cell therapy is shown in a table. (5 Refs)
Keywords: Burkitt's Lymphoma/IMMUNOLOGY/*THERAPY Cervix Neoplasms/IMMUNOLOGY/*THERAPY Female *Herpesvirus 4, Human Histocompatibility Antigens Class I/IMMUNOLOGY Human *HTLV-I *Immunotherapy Leukemia, T-Cell, Acute/IMMUNOLOGY/*THERAPY *Papillomavirus, Human Retroviridae Infections/*THERAPY T-Lymphocytes, Cytotoxic/IMMUNOLOGY/*TRANSPLANTATION Tumor Virus Infections/*THERAPY ABSTRACT
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
