CD81 is a novel immunotherapeutic target for B cell lymphoma

J Exp Med. 2019 Jul 1;216(7):1497-1508. doi: 10.1084/jem.20190186. Epub 2019 May 23.

Abstract

The tetraspanin CD81 was initially discovered by screening mAbs elicited against a human B cell lymphoma for their direct antiproliferative effects. We now show that 5A6, one of the mAbs that target CD81, has therapeutic potential. This antibody inhibits the growth of B cell lymphoma in a xenograft model as effectively as rituximab, which is a standard treatment for B cell lymphoma. Importantly, unlike rituximab, which depletes normal as well as malignant B cells, 5A6 selectively kills human lymphoma cells from fresh biopsy specimens while sparing the normal lymphoid cells in the tumor microenvironment. The 5A6 antibody showed a good safety profile when administered to a mouse transgenic for human CD81. Taken together, these data provide the rationale for the development of the 5A6 mAb and its humanized derivatives as a novel treatment against B cell lymphoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy / methods
  • Killer Cells, Natural / immunology
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Macrophages / immunology
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Rituximab / immunology
  • Rituximab / therapeutic use
  • Tetraspanin 28 / drug effects*
  • Tetraspanin 28 / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CD81 protein, human
  • Tetraspanin 28
  • Rituximab