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Extracellular domain of 4-1BBL enhanced the antitumoral efficacy of peripheral blood lymphocytes mediated by anti-CD3 x anti-Pgp bispecific diabody against human multidrug-resistant leukemia.

Research paper by Hongxing H Guo, Wenguo W Jiang, Wenge W Liu, Yingdai Y Gao, Ming M Yang, Yuan Y Zhou, Jinhong J Wang, Jing J Qi, Xin X Cheng, Zhenping Z Zhu, Chunzheng C Yang, Dongsheng D Xiong

Indexed on: 17 May '08Published on: 17 May '08Published in: Cellular Immunology



Abstract

Our previous data have shown a significantly higher tumor response to anti-CD3/anti-Pgp bispecific diabody-mediated immunotherapy for P-glycoprotein (Pgp)-overexpressing K562/A02 cells, but a rapid tumor relapse occurred at 1 week after therapy. In an attempt to overcome tumor recurrence, we supplemented the previous therapy with extracellular domain of human 4-1BBL (ex4-1BBL) to regulate the activation of peripheral blood lymphocyte (PBL). As a result, this combination showed enhanced cytotoxicity in vitro and eradicated the multidrug-resistant xenografts of K562/A02 in nude mice. Furthermore, no tumor recurrence was observed within 100 days after the first treatment. Therefore, when used as an adjuvant, ex4-1BBL may improve the outcome of PBL-based immunotherapy.