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 lymphokin e-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 a ntibody (MUSE11 mAb), directed to the MUC1 antigen, using N-succinimid yl 3-(2-pyridyldithio) propionate and 2-iminothiolane HCl. Both SEA-co njugated MUSE11 mAb (SEA-MUSE11) and the F(ab')(2) of MUSE11 mAb (SEA- F(ab')(2)) showed significant enhancement of T-LAK cell tumor neutrali zation for MUC1 positive-target tumor cells, even with a concentration of 0.01 mu g/ml at an E:T ratio of 5:1 in vitro, In this in vitro tes t, MUC1-positive BDC cells were observed to attach to surrounding T-LA K cells in the presence of SEA-MUSE11 or SEA-F(ab')(2). Remarkable tum or growth inhibition was observed in BDC-grafted severe combined immun odeficient mice to which 2 x 10(7) T-LAK cells preincubated with 2 mu g of SEA-MUSE11 or SEA-F(ab')(2), together with recombinant interleuki n 2 (500 IU), were administered i.v. for 4 consecutive days, when tumo r size was 5 mm in diameter. These results point to a promising adopti ve immunotherapy for patients with BDC.