Trioma-based vaccination against B-cell lymphoma confers long-lasting tumor immunity.
A major goal of tumor immunotherapy is the induction of a systemic immune response against tumor antigens such as the tumor-specific immunoglobulin idiotype (Id) expressed by lymphomas of the B-cell lineage. We describe an approach based on specific redirection of the tumor Id toward professional antigen-presenting cells (APCs), thereby overcoming the inefficient presentation on the parental transformed B cell. Lymphoma cells are fused to a xenogeneic hybridoma cell line that secretes an antibody against a surface molecule on APCs. Due to preferential assembly between heavy and light chains of antibodies of different species-origin, the resulting "trioma" cells produce at high yield a bispecific antibody containing the lymphoma Id and the APC-binding arm, which redirects the Id to APCs. Processing and presentation of the Id will lead to T-cell activation. An absolute requirement for inducing a complete tumor protection was the immunization with antibody-secreting trioma cells as a cell-based vaccine instead of the soluble bispecific antibody. Tumor immunity was specific and long-lasting. Both CD4+ and CD8+ T cells were necessary for inducing tumor immunity.
Mocikat
R
R
GSF-Institut für Immunologie, München, Germany. mocikat@gsf.de
Selmayr
M
M
Thierfelder
S
S
Lindhofer
H
H
D000818:Animals; D018033:Antibodies, Bispecific / Q000096:biosynthesis; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006825:Hybridomas; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D051381:Rats; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014611:Vaccination
D018033:Antibodies, Bispecific; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes