Description: B cell chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western hemisphere and, despite years of research, remains an incurable disease. Due to its relatively slow clinical progression, CLL is frequently described as a disease of accumulation rather than proliferation. Five years ago, however, researchers at the Feinstein Institute for Medical Research established that the leukemia cells from CLL patients proliferate at significant rates. Moreover, those patients with the highest proliferation were shown likely to suffer the most aggressive disease progression. Recent studies carried out at the Feinstein have further defined a number of cell surface markers that are expressed preferentially on cells of the CLL “proliferative compartment.” Based on these studies, The Feinstein researchers are in position to develop a “bi-specific” reagent – targeting both a cell surface antigen associated with CLL proliferation and a B cell-specific antigen – that would provide a novel method of selectively depleting this clinically-relevant proliferative subpopulation from patients with CLL.
This novel therapeutic approach to CLL is based on the following observations and hypothesis: CLL worsens over time as members of the clone develop new DNA mutations, “clonal evolution;” permanent DNA mutations can only be incorporated into the genome when cells divide; therefore, the proliferative compartment contains the most dangerous CLL cells and preferentially eliminating cells in the proliferative compartment would prevent clonal evolution and disease progression. Finally, by producing a bi-specific reagent, wherein at least one antigen is expressed solely or predominantly on human B lymphocytes, specific targeting for CLL will be assured.
Area of Application: Oncology – chronic lymphocytic leukemia (CLL), diagnostic/prognostic markers
Lead Investigator: Nicholas Chiorazzi, MD
Patent Info: Patent applications pending in the US as well as Australia, Canada and Europe
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