Effective adoptive immunotherapy by T-LAK cells retargeted with bacterial superantigen-conjugated antibody to MUC1 in xenografted severe combined immunodeficient mice

Masao Shinoda, Toshio Kudo, Masanori Suzuki, Yu Katayose, Naoki Sakurai, Hisaaki Saeki, Hideaki Kodama, Kenji Fukuhara, Kohzoh Imai, Yuji Hinoda, Seiki Matsuno

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Abstract

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 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.

Original languageEnglish
Pages (from-to)2838-2843
Number of pages6
JournalCancer Research
Volume58
Issue number13
Publication statusPublished - 1998 Jul 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Shinoda, M., Kudo, T., Suzuki, M., Katayose, Y., Sakurai, N., Saeki, H., Kodama, H., Fukuhara, K., Imai, K., Hinoda, Y., & Matsuno, S. (1998). Effective adoptive immunotherapy by T-LAK cells retargeted with bacterial superantigen-conjugated antibody to MUC1 in xenografted severe combined immunodeficient mice. Cancer Research, 58(13), 2838-2843.