4.7 Article

CD81 is a novel immunotherapeutic target for B cell lymphoma

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 7, Pages 1497-1508

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20190186

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Funding

  1. Translational Cancer Award from the Stanford Cancer Institute, Stanford's SPARK program
  2. Translational Cancer Award from the Stanford Cancer Institute, Stanford's Coulter program
  3. Breast Cancer Research program from the Department of Defense [W81XWH-14-1-0397]
  4. National Institutes of Health [5 R35 CA197353-04]
  5. American Society of Immunology through a Careers in Immunology fellowship

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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.

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