| First Author | Uckun FM | Year | 2015 |
| Journal | EBioMedicine | Volume | 2 |
| Issue | 4 | Pages | 306-316 |
| PubMed ID | 26097891 | Mgi Jnum | J:260531 |
| Mgi Id | MGI:6150552 | Doi | 10.1016/j.ebiom.2015.02.008 |
| Citation | Uckun FM, et al. (2015) Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand x Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-Resistant B-Precursor Acute Lymphoblastic Leukemia in Mice. EBioMedicine 2(4):306-316 |
| abstractText | In high-risk remission B-precursor acute lymphoblastic leukemia (BPL) patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT) even after use of very intensive total body irradiation (TBI)-based conditioning regimens, especially in patients with a high "minimal residual disease" (MRD) burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand x soluble TRAIL ("CD19L-sTRAIL") fusion protein. CD19L-sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI) combined with CD19L-sTRAIL was highly effective against (1) xenografted CD19(+) radiochemotherapy-resistant human BPL in NOD/SCID (NS) mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2) radiation-resistant advanced stage CD19(+) murine BPL with lymphomatous features in CD22DeltaE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L-sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT. |
