CD26 Protease Inhibition Improves Functional Response of Un-fractionated Cord Blood, Bone Marrow, and Mobilized Peripheral Blood Cells to CXCL12/SDF-1

Hematopoietic stem cell transplantation (HSCT) is an important treatment option for patients with malignant and non-malignant hematologic diseases. Methods to improve transplant efficiency are being explored with the intent of improving engraftment and immune reconstitution post-HSCT. A current approach under investigation involves treatment of donor cells with inhibitors that target the protease CD26, a negative regulator of the chemokine CXCL12/SDF-1. CD26 inhibitor treatment has been shown to improve the functional response of CD34 + cord blood (CB) cells but not CD34 + G-CSF mobilized PBSC to CXCL12/SDF-1. The effect of CD26 inhibitors on un-fractionated CB, bone marrow (BM), or G-CSF mobilized peripheral blood (mobPB) MNC has not previously been evaluated. We observed that although CB had greater CD26 expression than BM or mobPB, treatment with a CD26 inhibitor (Diprotin A) resulted in increased responsiveness to SDF-1 for all three MNC sources tested. This suggests that clinical therapeutic benefit may be gained to utilizing CD26 inhibitors as a strategy to improve engraftment of un-fractionated mobPB cells as well as CB cells.