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Vaccination against B-cell Chronic Lymphocytic Leukemia with Trioma Cells

Preclinical Evaluation¹

GSF-Institut für Molekulare Immunologie, München [U. W., E. N., H. P., H-J. K., R. M.]; Ludwig-Maximilians-Universität, Institut für Anthropologie und Humangenetik, München [R. G.] and Labor für Tumorimmunologie, Urologische Klinik, München [H. P.]; GSF-Institut für Klinische Molekularbiologie [M. S. S.]; Ludwig-Maximilians-Universität, Klinikum Großhadern, III. Medizinische Klinik [H-J. K., M. H.] and Genzentrum [M. H.]; and GSF, Klinische Kooperationsgruppe "Hämatopoetische Transplantation" [H-J. K.] and "Gentherapie," München [M. H.], Germany

Purpose: Trioma cells are lymphoma cells that have been fused to a hybridoma and have thereby been modified to express an immunoglobulin directed against surface receptors of antigen-presenting cells. Trioma cells that potentially include all lymphoma-derived antigens will be targeted to professional antigen-presenting cells in vivo. This allows uptake, processing, and presentation of tumor-derived antigens to T lymphocytes. In a mouse model, vaccination with trioma cells conferred long-lasting, T cell-dependent tumor immunity and was even able to eradicate established lymphomas. Here, we investigated whether this potent approach is effective in the human system.

Experimental design: Malignant cells from 11 patients with B cell chronic-lymphocytic leukemia (B-CLL) were fused to an anti-Fc receptor hybridoma. The resulting trioma cells were extensively characterized with respect to their clonal origin. The induction of autologous tumor-specific T lymphocytes in the presence of trioma and antigen-presenting cells was examined in vitro by determining cytokine secretion in coculture assays.

Results: In seven cases, trioma cells could successfully be generated from B-CLL cells. Stimulation of autologous lymphocytes with trioma cells induced a leukemia-specific T-cell response. Immunostimulatory trioma cells were also obtained from two patients with solid B-cell lymphoma.

Conclusions: Trioma-mediated immunization may be a promising adjuvant treatment of human malignancies of the B-cell lineage, particularly of B-CLL, which has still a very poor prognosis. Our in vitro results pave the way for clinical application.