Scripps study uncovers novel CLL drug target
Scientists at The Scripps Research Institute have discovered a previously unreported cell surface antigen which provides a promising new immunotherapy target to treat patients with chronic lymphocytic leukemia (CLL). The target, Siglec-6, was identified using Retrogenix cell microarray screening after attempts to uncover the antigen by immunoprecipitation and mass spectrometry proved unsuccessful.
CLL is the most common form of leukemia in the U.S. which currently can only by cured by allogeneic haematopoietic stem cell transplantation (alloHSCT). Although alloHSCT is a risky therapy, its effectiveness is most likely due to post-transplantation antibodies – that are specific to CLL antigens – promoting an immune response to the disease.
To uncover a potential immunotherapy target that could ultimately replace the need for stem cell transplantation, post-alloHSCT antibodies were selected, enriched and then screened for interactions against thousands of membrane protein receptors over-expressed in human cells. Siglec-6 was the strongest hit from these cell microarray studies and was subsequently verified as a CLL-specific antigen.
- Unveiled Siglec-6 as a broadly expressed CLL cell surface antigen and a candidate target for immunotherapy
- Revealed that endogenous antibodies to Siglec-6 are safe
- Delivered fully human anti-human Siglec-6 monoclonal antibodies
The project, led by Scripps, was undertaken in collaboration with Retrogenix and the US National Institutes of Health. To view the paper abstract and full text options please click here.