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

Tohoku J Exp Med. 1996 Feb;178(2):113-27. doi: 10.1620/tjem.178.113.

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 combination with (OK x L) BsAbs should be very promising.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • Antibody Specificity
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / immunology
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Humans
  • Immunotoxins / pharmacology*
  • Phenotype
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Cells, Cultured

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunotoxins
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue