Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response.
The anti-CD20 monoclonal antibody (mAb) rituximab has been used successfully for lymphoma therapy for more than 10 years. Although several direct mechanisms by which anti-CD20 mAbs act have been characterized in vitro, their specific role in clinical efficacy is still debated. Little is known about the possible antitumor immune response that they may induce in patients, despite clinical data suggesting a "vaccinal" effect. We show here that an initial treatment with anti-CD20 induces protection against human CD20-expressing tumor cells and allows immunocompetent mice to survive tumor challenge. This long-lasting protection requires the presence of the Fc portion of the anti-CD20 mAb and is achieved through the induction of a cellular immune response. Only CD4(+) cells were needed at the beginning of the treatment, but both CD4(+) and CD8(+) cells were required after tumor challenge to achieve protection. Finally, we show that interleukin-2 treatment, given after tumor challenge, improves the overall survival rate, compared with that obtained by anti-CD20 treatment alone. These findings demonstrate that anti-CD20 mAbs exert therapeutic effects through the induction of an adaptive cellular immune response, aside from any direct mechanisms involving effectors from innate immunity.
Abès
Riad
R
INSERM Unite Mixte de Recherche (UMR) S872, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, 15 rue de l'Ecole de Medecine, Paris, France.
Gélizé
Emmanuelle
E
Fridman
Wolf Herman
WH
Teillaud
Jean-Luc
JL
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D015478:Antigens, Heterophile / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D000069283:Rituximab; D015996:Survival Rate; D013945:Thymoma / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D013953:Thymus Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D013997:Time Factors
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015478:Antigens, Heterophile; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007141:Immunoglobulin Fc Fragments; D007376:Interleukin-2; D000069283:Rituximab