A novel NOD.SCID mouse model suggests CD200-mediated regulation may be important for both growth and therapy of CLL (165.36)

Abstract

Abstract Chronic lymphocytic leukemia is characterized by the accumulation of malignant CD5+CD19+ B cells that, like anergic B cells, typically fail to engraft in immunocompromised murine hosts. CD200, a type I transmembrane molecule with potent immunoregulatory functions, is known to be overexpressed on CLL cells. Using a CD200 sandwich-ELISA, we have identified a soluble form of CD200 (sCD200), whose expression is increased by >5-fold in the serum of CLL patients compared to healthy controls. Further analysis of sCD200 levels in CLL patient serum showed a correlation between sCD200 levels and Rai disease stage. Infusion of sCD200hi CLL serum into NOD.SCIDIL-2γ-/- mice receiving 1x108 CLL splenocytes enhanced engraftment of CLL cells, which were detectable in both the spleen and peritoneum of animals, in comparison to mice receiving sCD200lo normal serum. Enhanced engraftment using CLL serum was abrogated by depletion of sCD200 from the serum. When given at 21 days post-CLL splenocyte infusion, anti-CD200mAb was as effective as Rituximab in eliminating engrafted CLL. In vivo T cell depletion with anti-CD3mAb also suppressed CLL engraftment, despite ongoing CLL serum infusion, suggesting that T cells are important to maintain CLL survival and growth. Our studies show that infusion of sCD200hi CLL serum into NOD.SCID mice allows development of a novel xenograft model for CLL, and further suggest that anti-CD200 mAb may have value in treatment of disease.