Anti-GD3 monoclonal antibody effects on lymphocytes and antibody-dependent cellular cytotoxicity.
OBJECTIVE
Antibodies targeting GD3 gangliosides highly expressed on melanomas mediate immune effector functions in vitro and inhibit animal model melanoma tumor growth in vivo. Because GD3 is expressed also on a subpopulation of human lymphocytes, we characterized the in vitro immune effects of murine R24 and a chimeric anti-GD3 antibody (KW-2871).


METHODS
Anti-GD3 complement-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested against cell line Mel-624. Antibody-mediated lymphocyte expression of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) was quantified. The effect of antibody and antibody-treated lymphocyte supernates on effector cell ADCC and Fc receptor expression were evaluated.


RESULTS
R24 and KW-2871 antibodies mediated CMC and ADCC to the Mel-624 cell line. R24 induced potent lymphocyte proliferation and enhanced lymphocyte RNA expression of IL-4 (2-4 logs), IL-10, and IFN-gamma (> 10-fold). KW-2871 induced no lymphocyte proliferation and had minimal effects on lymphokine expression (< 5-fold). Preincubation of effector cells with either antibody inhibited ADCC and reduced monocyte expression of FcgammaRI and II. Supernates of effector cells preincubated with either antibody were able to inhibit ADCC.


CONCLUSIONS
R24 and KW-2871 antibody differ in their lymphocyte proliferation and lymphokine release activity but have similar inhibition of lymphocyte ADCC and FcgammaR expression in vitro.
Triozzi
Pierre L
PL
Department of Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294-3300, USA.
Shah
Jatin J
JJ
Wang
Wen-Quan
WQ
Aldrich
Wayne
W
Edberg
Jeffrey C
JC
Su
Kaihong
K
Carlisle
Ronda
R
Conry
Robert
R
LoBuglio
Albert F
AF
Forero
Andres
A
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000633:toxicity*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016207:Cytokines; D005732:Gangliosides; D012333:RNA, Messenger; D011961:Receptors, Fc; C026226:ganglioside, GD3