Tumor-associated glycoantigen, sialyl Lewis(a) as a target for bispecific antibody-directed adoptive tumor immunotherapy.
The KM231 mAb recognizing sialyl Lewis(a) (sLe(a)) epitope of glycoprotein or glycolipid expressed on various human cancers was used to prepare bispecific antibody (BSAb) containing anti-CD3 x anti-sLe(a) mAb. The effect of anti-CD3 x anti-sLe(a) BSAb on the induction of cytotoxicity by activated T cells was investigated. The activated CD3+ T cells expressing CD8 or CD4 were induced from human peripheral blood mononuclear cells by culture with recombinant IL-2 plus immobilized anti-CD3 mAb. The activated CD8+ and CD4+ T cells showed marginal cytotoxicity against tumor cells by themselves. However, addition of anti-CD3 x anti-sLe(a) BSAb resulted in a great augmentation of their cytotoxicity against gastrointestinal tumor cells. The BSAb also triggered IL-2 production of CD4+ helper/killer T cells during lysis of tumor cells. Moreover, the BSAb was demonstrated to have a potent in vivo antitumor activity against human colon cancer implanted in nude mice by combination with CD4+ helper/killer cells. These results demonstrated that sLe(a) antigen might be a good target molecule for BSAb-directed adoptive tumor immunotherapy.
Ohta
S
S
Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Tsukamoto
H
H
Watanabe
K
K
Makino
K
K
Kuge
S
S
Hanai
N
N
Habu
S
S
Nishimura
T
T
D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D018395:CA-19-9 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
D018033:Antibodies, Bispecific; D015295:Antigens, Tumor-Associated, Carbohydrate; D018395:CA-19-9 Antigen; D005732:Gangliosides; D007376:Interleukin-2; D007983:Lewis Blood Group Antigens; C064564:sialyl Le(a) ganglioside