Vaccination against B-cell chronic lymphocytic leukemia with trioma cells: preclinical evaluation.
OBJECTIVE
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.


METHODS
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.
D000328:Adult; D000368:Aged; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines; D016207:Cytokines