All Publications


  • Development of multivalent CAR T cells as dual immunotherapy and conditioning agents MOLECULAR THERAPY ONCOLOGY Bubb, Q., Balood, M., Seir, G., Swartzrock, L., Haslett, E., Ho, K., Xu, P., Wiltz, S. G., Sotillo, E., Gruber, T. A., Richards, R. M., Mackall, C. L., Czechowicz, A. 2025; 33 (1)
  • Development of multivalent CAR T cells as dual immunotherapy and conditioning agents. Molecular therapy. Oncology Bubb, Q. R., Balood, M., Seir, G. E., Swartzrock, L., Haslett, E., Ho, K., Xu, P., Wiltz, S. G., Sotillo, E., Gruber, T. A., Richards, R. M., Mackall, C. L., Czechowicz, A. 2025; 33 (1): 200944

    Abstract

    Hematopoietic stem cell transplantation (HSCT) is the only definitive cure for pediatric acute myeloid leukemia (AML). Despite adjustments in HSCT protocols and improvements in supportive care, 30% of high-risk patients who receive HSCT as part of their therapy still experience disease relapse with high transplant-related mortality. Relapsed AML has a dismal prognosis, and novel therapies are needed. To improve upon the status quo, HSCT would more effectively eliminate relapse-initiating leukemic cells and be delivered with safer, non-genotoxic conditioning. Here, we investigate hematopoietic cytokine receptors (HCRs) and identify that KIT, MPL, and FLT3 are collectively highly expressed in virtually all pediatric AML samples studied. Further, we establish proof-of-concept of a first-in-class chimeric antigen receptor (CAR) T cell that enables simultaneous targeting of KIT, MPL, and FLT3 through a single receptor, which we term the extracellularly linked concatemeric trivalent cytokine (ELECTRIC) CAR. ELECTRIC CARs exhibit potent cytotoxicity against normal and malignant hematopoietic cells in vitro and display anti-HCR activity in a murine xenograft model. We propose that the ELECTRIC system can be the foundation to developing a non-genotoxic, anti-leukemic conditioning regimen to enable safer, more durable efficacy with minimal toxicity.

    View details for DOI 10.1016/j.omton.2025.200944

    View details for PubMedID 40034967

    View details for PubMedCentralID PMC11872492

  • Development of Extracellularly Linked Concatemeric Trivalent Cytokine (ELeCTriC) Chimeric Antigen Receptor (CAR) T-Cells as Dual Conditioning and Immunotherapeutic Agents Bubb, Q. R., Balood, M., Seir, G. E., Swartzrock, L., Haslett, E., Ho, K., Wiltz, S. G., Sotillo, E., Richards, R. M., Gruber, T. A., Mackall, C. L., Czechowicz, A. CELL PRESS. 2024: 75