Comparison of in vitro antibody-targeted cytotoxicity using mouse, rat and human effectors |
| |
Authors: | Ira Bergman Per H Basse Mamdouha A Barmada Judith A Griffin Nai-Kong V Cheung |
| |
Institution: | (1) University of Pittsburgh Medical Center, Pittsburgh, Pa., US,;(2) Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pa 15213, USA e-mail: bergmai@chplink.chp.edu Tel.: +1-412-692-6182; Fax: +2-412-692-6787, US;(3) Memorial Sloan Kettering Cancer Center, New York, N.Y., USA, US |
| |
Abstract: | Antibodies can direct tumor cell lysis by activating complement-mediated and cell-mediated cytoxicities (antibody-dependent
cell-mediated cytotoxicity, ADCC). Clinical translation of these effects into successful cancer therapy has been slow. Choosing
an appropriate animal model to test new therapeutic strategies is difficult because of species differences in immunological
effector functions. In previous work, we found that an unmodified anti-ganglioside mouse IgG3 monoclonal antibody (mAb), 3F8,
could successfully treat clinical tumors in humans and experimental tumors in rats but not experimental tumors in mice. We
explored the reasons for this species difference by performing in vitro antibody-dependent cytotoxicity assays comparing the
potency of polymorphonuclear neutrophils (PMN), natural killer (NK) cells and complement from the three species: mouse, rat
and human. 3F8-dependent complement-mediated cytotoxicity produced more than 70% specific release when human and rat sera
were used and only 20% with mouse serum. PMN-mediated ADCC was 35%–70% with human effectors, 25%–60% with rat and undetectable
with mouse. Human eosinophils did not contribute to this ADCC. Cytotoxicity utilizing interleukin-2-activated NK cells was
antibody-independent in all three species but the specific release was 60%–70% with human and rat NK cells and 10% with mouse
NK cells. These data suggest that, for mouse IgG3, the rat may provide a more relevant rodent model than the mouse for testing
the in vivo antitumor effects of monoclonal antibodies.
Received: 20 January 2000 / Accepted: 24 March 2000 |
| |
Keywords: | Antibody-dependent cytotoxicity Complement Neutrophils Eosinophils |
本文献已被 PubMed SpringerLink 等数据库收录! |
|