Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 7, Pages 1497-1508Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20190186
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Funding
- Translational Cancer Award from the Stanford Cancer Institute, Stanford's SPARK program
- Translational Cancer Award from the Stanford Cancer Institute, Stanford's Coulter program
- Breast Cancer Research program from the Department of Defense [W81XWH-14-1-0397]
- National Institutes of Health [5 R35 CA197353-04]
- 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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