Effective adoptive immunotherapy by T-LAK cells retargeted with bacterial superantigen-conjugated antibody to MUC1 in xenografted severe combined immunodeficient mice.
To reinforce cytotoxic activity and the targeting ability of lymphokine-activated killer cells with a T-cell phenotype (T-LAK) for adoptive immunotherapy against human bile duct carcinoma (BDC), staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 monoclonal antibody (MUSE11 mAb), directed to the MUC1 antigen, using N-succinimidyl 3-(2-pyridyldithio) propionate and 2-iminothiolane HCl. Both SEA-conjugated MUSE11 mAb (SEA-MUSE11) and the F(ab')2 of MUSE11 mAb (SEA-F(ab')2) showed significant enhancement of T-LAK cell tumor neutralization for MUC1 positive-target tumor cells, even with a concentration of 0.01 microg/ml at an E:T ratio of 5:1 in vitro. In this in vitro test, MUC1-positive BDC cells were observed to attach to surrounding T-LAK cells in the presence of SEA-MUSE11 or SEA-F(ab')2. Remarkable tumor growth inhibition was observed in BDC-grafted severe combined immunodeficient mice to which 2 x 10(7) T-LAK cells preincubated with 2 microg of SEA-MUSE11 or SEA-F(ab')2, together with recombinant interleukin 2 (500 IU), were administered i.v. for 4 consecutive days, when tumor size was 5 mm in diameter. These results point to a promising adoptive immunotherapy for patients with BDC.
Shinoda
M
M
First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
Kudo
T
T
Suzuki
M
M
Katayose
Y
Y
Sakurai
N
N
Saeki
H
H
Kodama
H
H
Fukuhara
K
K
Imai
K
K
Hinoda
Y
Y
Matsuno
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000628:therapy*; D002448:Cell Adhesion; D004768:Enterotoxins / Q000627:therapeutic use*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000922:Immunotoxins / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000276:immunology*; D009368:Neoplasm Transplantation; D018089:Superantigens / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D000922:Immunotoxins; D018396:Mucin-1; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal