Hybrid Cell Vaccination in Patients With Metastatic Melanoma

Hybrid cell vaccination is a novel approach for immunotherapy of cancers by inducing specific antitumor immunity (1 ,2 ). The hybrid cells are generated by electrofusing autologous tumor cells with allogeneic MHC class II expressing cells such as B lymphocytes. The fused cells are irradiated and injected subcutaneously as a vaccine. This immune therapeutical approach aims at recruitment of T-cell help for the induction of tumor-specific cytolytic immunity. It is based on the observation that epitope linkage is a prerequisite for productive T-T cell collaboration, i.e., cytolytic precursor and helper T cells have to be activated by the same antigen presenting cell that displays epitopes for both T-cell types on the corresponding MHC class I and class II molecules (3 ,4 ). Neither of the two epitopes nor the corresponding T cells need to be related. The implications of this concept are, first, only MHC class I and II expressing cells can induce cytolytic T-cell responses (5 -7 ), second, cognate antigens must be presented for both T-cell and MHC types (4 ,8 ) and, third, there must be T cells with the corresponding specificities in the T-cell receptor repertoire of the response-competent individual.