Cross-priming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies?
Humanizing xenogenic monoclonal antibodies (MAbs) by genetic engineering has greatly improved their therapeutic utility and efficacy. The chimeric CD20 MAb C2B8 (Rituximab) is a prominent representative of this new generation of therapeutic MAbs and has been proposed as a treatment of choice for recurrent follicular non-Hodgkin's lymphomas. Treatment of CD20+ B cells with MAb C2B8 triggers several cell-damaging actions including complement-mediated lysis (CDL), antibody-dependent cellular cytotoxicity (ADCC), and MAb-induced induction of apoptosis. We provide an overview of the most prominent mechanisms underlying the efficacy of antibody treatment. We introduce our concept of cross-priming of cytotoxic T-cell responses promoted by apoptosis incucing antibodies. Treatment of tumor cells with antibodies that are capable of inducing a proapoptotic signal via their cell surface target structure may not only contribute to their direct killing but also may induce cellular responses against the tumor, which may have a long-lasting protective effect. We report, using the example of C2B8 anti-CD20 treatment of lymphoma cells, that MAb C2B8-induced apoptosis of lymphoma cells not only kills these cells but also promotes uptake and cross-presentation of lymphoma cell-derived peptides by antigen-presenting dendritic cells (DC), induces maturation of DC, and allows the generation of specific CTL.
Selenko
Nicole
N
Institute of Immunology, University of Vienna, Medical School, Austria.
Majdic
Otto
O
Jäger
Ulrich
U
Sillaber
Christian
C
Stöckl
Johannes
J
Knapp
Walter
W
D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000910:Antibodies, Heterophile; D000912:Antibodies, Neoplasm