The antitumor activity induced by the in vivo administration of activated B cells bound to anti-CD3 monoclonal antibody.
We examined the immunotherapeutic ability of activated B cells which bound to anti-CD3 monoclonal antibody (mAb) to enhance antitumor T cell immunity in vivo. A flow cytometric analysis revealed that LPS (lipopolysaccharide)-activated B cells (LPS blasts) expressed Fc receptor (FcR) which can bind to anti-CD3 mAb. LPS blasts were also stained with CTLA-4Ig, which can bind to costimulation molecules with high affinity, which suggested that LPS blasts expressed costimulation molecules on their surface. In an in vitro assay, T cells remarkably proliferated in the presence of LPS blasts and soluble anti-CD3 mAb, whereas this proliferation was blocked by the addition of CTLA-4Ig. In a model of metastasis established by the intravenous inoculation of melanoma cells, the in vivo administration of LPS blasts incubated with anti-CD3 mAb and followed by treatment with polyethylene glycol, to reinforce the binding, induced a low but significant antitumor activity against melanoma. The antitumor activity induced by the in vivo administration of LPS blasts which bound to anti-CD3 mAb was also detected in the spontaneously established model of metastasis. These results therefore suggest that the in vivo administration of activated B cells which bound to anti-CD3 mAb was able to enhance the antitumor T cell response against metastatic melanoma.
Harada
M
M
Department of Virology, Kyushu University, Fukuoka, Japan.
Okamoto
T
T
Kurosawa
S
S
Shinomiya
Y
Y
Ito
O
O
Takenoyama
M
M
Terao
H
H
Matsuzaki
G
G
Kimura
G
G
Nomoto
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex