The Spiegelmer® Nox-A12
Hinterseer E, Girbl T, Hutterer E et al.
Key Points:
- Investigators aimed to compare efficacy of NOX-A12 (specific chemokine SDF-1 antagonist) and AMD3100 (CXCR4 antagonist) to mobilize CLL cells from their protective niches to peripheral blood, thereby sensitizing them to cytotoxic agents and to prevent their recirculation into protective lymphoid microenvironment
- In majority of investigated CLL samples, CXCR4/SDF-1 inhibition reduced CLL cell recirculation into BM, thereby redirecting them into spleen (except trisomy 12)
- CLL cells homed to bone marrow expressed elevated CXCR4 surface levels and CXCR4 levels further increased upon CXCR4/SDF-1 inhibition with NOX-A12 and AMD3100
- Experiments in mice treated with NOX-A12 & AMD3100: CLL cell blood count raised from 80% to 120% within 6 hours even with low doses and higher doses led to prolonged mobilization duration
- AMD3100 treatment did not lead to significant increase in CLL cell or total lymphocyte blood count in peripheral blood.
Implications:
- Current study demonstrates high efficiency of NOX-A12 to mobilize CLL cells and to prevent their recirculation into protective lymphatic organs.
Additional Comments:
- Investigators currently evaluating effect of combined NOX-A12 and fludarabine treatment on progression and overall survival in Tcl1 transgenic transplantation model.
View the original abstract on the ASH website.
