Tumor-associated glycoantigen, sialyl Lewis(a) as a target for bispecific antibody-directed adoptive tumor immunotherapy

Immunol Lett. 1995 Jan;44(1):35-40. doi: 10.1016/0165-2478(94)00177-s.

Abstract

The KM231 mAb recognizing sialyl Lewis(a) (sLe(a)) epitope of glycoprotein or glycolipid expressed on various human cancers was used to prepare bispecific antibody (BSAb) containing anti-CD3 x anti-sLe(a) mAb. The effect of anti-CD3 x anti-sLe(a) BSAb on the induction of cytotoxicity by activated T cells was investigated. The activated CD3+ T cells expressing CD8 or CD4 were induced from human peripheral blood mononuclear cells by culture with recombinant IL-2 plus immobilized anti-CD3 mAb. The activated CD8+ and CD4+ T cells showed marginal cytotoxicity against tumor cells by themselves. However, addition of anti-CD3 x anti-sLe(a) BSAb resulted in a great augmentation of their cytotoxicity against gastrointestinal tumor cells. The BSAb also triggered IL-2 production of CD4+ helper/killer T cells during lysis of tumor cells. Moreover, the BSAb was demonstrated to have a potent in vivo antitumor activity against human colon cancer implanted in nude mice by combination with CD4+ helper/killer cells. These results demonstrated that sLe(a) antigen might be a good target molecule for BSAb-directed adoptive tumor immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • CA-19-9 Antigen / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / transplantation*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytotoxicity Tests, Immunologic
  • Flow Cytometry
  • Gangliosides / immunology*
  • Humans
  • Interleukin-2 / biosynthesis
  • Lewis Blood Group Antigens / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / immunology*
  • Neoplasms / therapy*

Substances

  • Antibodies, Bispecific
  • Antigens, Tumor-Associated, Carbohydrate
  • CA-19-9 Antigen
  • Gangliosides
  • Interleukin-2
  • Lewis Blood Group Antigens
  • sialyl Le(a) ganglioside