A new in vitro model of specific targeting therapy of cancer: retargeting of PWM-LAK cells with bispecific antibodies greatly enhances cytotoxicity to hepatocellular carcinoma.
For the purpose of establishing a new in vitro model of adoptive immunotherapy, we synthesized two kinds of bispecific antibodies (BsAbs), i.e., (OK x L) BsAbs constructed with both OKT-3 (anti-CD3) and L-7-6 (anti-HCC), and (3G x L) BsAbs constructed with 3-G-8 (anti-CD16) and L-7-6 antibodies. These two BsAbs, having pairs of binding arms on their single molecule, showed similar binding to target cells as the parental monoclonal antibodies (OKT-3, 3-G-8 and L-7-6), when examined with FACS. Newly devised in vitro cytotoxicity tests revealed that LAK or PWM-stimulated LAK (PWM-LAK) cells did not show any significant cytotoxic activity to HCC cells, while both effector cells equally showed greatly enhanced cytotoxicity to HCC even at a low effector/target (0.3) in the presence of BsAbs (OK x L) for the efficient retargeting of the effector cells. Inasmuch as PWM-LAK cells proliferate in vitro 3-5 times faster than LAK cells, adoptive immunotherapy using PWM-LAK cells in combination with (OK x L) BsAbs should be very promising.
Saijyo
S
S
First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
Kudo
T
T
Katayose
Y
Y
Saeki
H
H
Chiba
N
N
Suzuki
M
M
Tominaga
T
T
Matsuno
S
S
D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000922:Immunotoxins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue