Enhancement of cytotoxic and proliferative responses of lymphocytes from melanoma patients by incubation with monoclonal antibodies against ganglioside GD3.
Previous studies have shown that monoclonal antibodies (M.Ab) to the ganglioside GD3 may induce partial remissions in tumour growth in patients with melanoma. In vitro studies demonstrated that M.Abs to GD3 may also enhance lymphocyte responses to phytohemagglutinin and interleukin 2 (IL2). The present study extended these findings by showing that the IL2-dependent proliferative and cytotoxic response of T cell clones derived from a melanoma patient and a patient with the Vogt-Koyanagi-Harada syndrome were enhanced by pre-incubation of T cells with M.Ab to GD3. The degree of enhancement increased with the duration of pre-incubation from 2 to 24 h and applied to both T4+ and T8+ clones. The potentiation of these responses was not specific for M.Abs to GD3 but was also seen with M.Abs to GD2 and the T10 structure on T cells but not with M.Abs to the transferrin receptor or an isotype control M.Ab. Incubation of lymphocytes from a melanoma patient with M.Ab to GD3 during culture with autologous melanoma cells enhanced the proliferative response to the tumour. The expression of IL2 receptors (Tac epitope) on the T cells showed variable enhancement after incubation with M.Ab to GD3 but the significance of these findings in relation to the mechanism of the enhanced responses is not known. These results suggest that certain M.Abs may stimulate cell-mediated immune responses against tumour cells and that this may provide an additional mode of action of M.Abs against tumours in vivo.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007376:Interleukin-2; C026226:ganglioside, GD3