The central hypothesis of this proposal is that an effective anti-lymphoma response can be initiated by presentation of the tumor specific idiotype in an appropriate form to T helper cells by non-tumor antigen presenting cells. This further implies that tumor cells are not normally able to present antigens effectively to the immune system. B cell lymphomas were selected as a model system for these studies since these are among the only human tumors for which a tumor specific antigen (immunoglobulin idiotype) has been identified. Both Burkitt's and follicular lymphomas will be investigated for the following reasons: 1) both express cell surface idiotype, 2) Burkitt's lymphomas are relatively easy to grow in vitro, providing an essentially unlimited source of tumor, 3) we have recently established methods for the in vitro propagation of follicular lymphomas, a much more prevalent type of lymphoma, and 4) the autologous cytotoxic T cell response to these two types of lymphoma is quite different. T helper cells both initiate and regulate the immune response. Characterization of the autologous helper T cell response to tumor idiotype should allow the development of methods to improve this response in vivo to prevent tumor .growth. T helper cell lines and clones specific for autologous tumor will be derived and used to define particular epitopes of the immunoglobulin molecule required for activation, the roles of MHC and accessory molecules in antigen presentation, and the particular cytokines and cytokine receptors expressed by these cells. This information will be used to develop methods to improve the helper T cell response to idiotype determinants presented by non-tumor antigen presenting cells. Methods to enhance both antigen presentation and the T cell response are proposed. These studies will give insights into the immune recognition of tumor specific antigens and provide strategies for the construction of cancer vaccines.
| Nelson, E L; Kim, H T; Mar, N D et al. (1995) Novel tumor-associated accessory molecules involved in the gamma/delta cytotoxic T-lymphocyte-Burkitt's lymphoma interaction. Cancer 75:886-93 |
