APPROACH # 1

Our new approach could significantly enhance the efficacy and safety of CAR T-cell therapies for AML and potentially other myeloid neoplasms.

  1. Gene-Edited Hematopoietic Stem and Progenitor Cells (HSPCs): We propose using gene-edited HSPCs that lack the antigen to be targeted by CAR T cells for example CD33 antigen. By creating CD33 knockout (KO) HSPCs, a myeloid system can be regenerated that is resistant to CD33-targeted therapies.
  2. Antigen-Specific Immunotherapy: This innovative approach allows for the administration of potent antigen-directed therapy (specifically targeting CD33) without inducing prolonged myeloid aplasia, thus sparing normal hematopoiesis.
  3. Combination Therapy: Our approach includes combining allogeneic transplantation of CD33 KO HSPCs with CD33 CAR T cell therapy. This dual strategy aims to effectively treat patients with otherwise incurable AML while minimizing the risk of damaging normal blood cells.

Reconstitution of the immune system with CD33-negative human hematopoietic stem cells enables anti- CD33 CAR-T cell killing of acute myeloid leukemia while sparing myeloid development and function.

 

We have launched a clinical trial based on this approach. CD33KO-HSPC Infusion Followed by CART-33 Infusion(s) for Refractory/​Relapsed AML (CART33). To learn more about this trial please visit ClinicalTrials.gov ID NCT05945849.