P-ckit-ALLO1

Conditioning regimens typically consist of high doses of genotoxic radiation or busulfan that can lead to life-threatening post-transplant complications. Our data indicate that anti-c-kit CAR-T cells can be used as an alternative and less toxic conditioning regimen to facilitate engraftment of autologous HSCs. Future studies aim to further develop our humanized transplant model to assess their use in an allogeneic HSC transplant setting.

These conditioning regimens typically consist of high doses of genotoxic radiation or busulfan that can lead to life-threatening post-transplant complications. To compare the activity of CAR 1 and CAR 2 in a transplant model we are currently performing a full allogeneic transplant study in huNSG mice involving CAR-T cell-mediated depletion of engrafted human stem cells, safety switch activation to clear the CAR-T cells, followed by engraftment of second donor CD34+ cells. We anticipate our results will provide additional strong evidence for use of stem cell-directed CAR-T cells as an alternative and less toxic conditioning regimen to facilitate engraftment of allogeneic and gene-corrected autologous HSCs and to significantly broaden the number of patients eligible for transplant.