A new in vitro model of specific targeting therapy of cancer: Retargeting of PWM-LAK cells with bispecific antibodies greatly enhances cytotoxicity to hepatocellular carcinoma

Susumu Saijyo, Toshio Kudo, Yu Katayose, Hisaaki Saeki, Natsuko Chiba, Masanori Suzuki, Tsuyoshi Tominaga, Seiki Matsuno

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

For the purpose of establishing a new in vitro model of adoptive immunotherapy, we synthesized two kinds of bispecific antibodies (BsAbs), i.e. (OK x L) BsAbs constructed with both OKT-3 (anti-CD3) and L-7-6 (anti-HCC), and (3G x L) BsAbs constructed with 3-G-8 (anti-CD16) and L-7-6 antibodies. These two BsAbs, having pairs of binding arms on their single molecule, showed similar binding to target cells as the parental monoclonal antibodies (OKT-3, 3-G-8 and L-7-6), when examined with FACS. Newly devised in vitro cytotoxicity tests revealed that LAK or PWM-stimulated LAK (PWM-LAK) cells did not show any significant cytotoxic activity to HCC cells, while both effector cells equally showed greatly enhanced cytotoxicity to HCC even at a low effector/target (0.3) in the presence of BsAbs (OK x L) for the efficient retargeting of the effector cells. Inasmuch as PWM-LAK cells proliferate in vitro 3-5 times faster than LAK-cells, adoptive immunotherapy using PWM-LAK cells in combinations with (OK x L) BsAbs should be very promising.

Original languageEnglish
Pages (from-to)113-127
Number of pages15
JournalTohoku Journal of Experimental Medicine
Volume178
Issue number2
DOIs
Publication statusPublished - 1996 Feb

Keywords

  • PWM-LAK cells
  • adoptive immunotherapy
  • bispecific antibody
  • hepatocellular carcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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