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Effective Adoptive Immunotherapy by T-LAK Cells Retargeted with Bacterial Superantigen-conjugated Antibody to MUC1 in Xenografted Severe Combined Immunodeficient Mice¹

First Department of Surgery, Tohoku University School of Medicine [M. Sh., M. Su., Y. K., N. S., H. K., K. F., S. M.] and Cell Resource Center for Biomedical Research, Institute of Development, Aging, and Cancer, Tohoku University, [T. K., H. S.], Sendai 980-8575, and Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-0061 [K. I., Y. H.], Japan

To reinforce cytotoxic activity and the targeting ability of lymphokineactivated 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 µg/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 10⁷ T-LAK cells preincubated with 2 µg 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.

¹ This work was supported in part by Grant-in-Aid for Cancer Research 06279101 from the Ministry of Education, Science, Sports and Culture of Japan.

² To whom requests for reprints should be addressed, at the Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan. Fax: 81-22-717-8573.

Received 10/13/97. Accepted 5/ 1/98.

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