General AML

The FDA grants CD33-specific CAR+ T cell Investigational New Drug Application clearance for treatment of R/R AML

On 2nd May 2017, the U.S. Food and Drug Administration (FDA) accepted the Investigational New Drug (IND) application and granted clearance for  CD33-specific Chimeric Antigen Receptor (CAR) +  T-cell therapy for patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML).1

CD33-specific CAR+ T-cell is a lentiviral construct that co-expresses CD33-specific CAR and a kill switch based on a tag derived from the epidermal growth factor receptor, which allows for the conditional elimination of CAR-T cells in vivo. CD33 is a transmembrane protein expressed on normal and malignant myeloid-derived cells. In AML blasts, CD33 is broadly expressed and high levels of CD33 expression is associated with poor survival outcomes in AML patients. 2 Preclinical analysis of CD33 CAR-T cells in CD33+ AML cell lines have demonstrated specific cytotoxicity.3

The IND approval granted by the FDA allows CD33-speciifc CAR T-cell to be evaluated in phase I clinical trial (NCT03126864) in R/R AML patients which is now active. In this study, the safety and tolerability of three different doses of CD33-CAR T-cell would be evaluated in CD33+ patients with R/R AML. Treatment of the first patient enrolled in this study is anticipated to begin in June 2017.1

References
  1. GlobeNewswire: ZIOPHARM Oncology Announces FDA Acceptance of IND for CD33-Specific CAR-T Cell Therapy Targeting Relapsed/Refractory Acute Myeloid Leukemia. 2017 May 02. https://globenewswire.com/news-release/2017/05/02/975428/0/en/ZIOPHARM-Oncology-Announces-FDA-Acceptance-of-IND-for-CD33-Specific-CAR-T-Cell-Therapy-Targeting-Relapsed-Refractory-Acute-Myeloid-Leukemia.html [Accessed 2017 May 04].
  2. Laszlo G.S. et al. The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev. 2014 Jul: 28(4): 143–53. DOI: 10.1016/j.blre.2014.04.001. Epub 2014 Apr 21.
  3. Song D. et al. Chimeric Antigen Receptor-Modified T Cells for the Treatment of Acute Myeloid Leukemia Expressing CD33. Abstract #4058: ASH 58th Annual Meeting and Exposition, San Diego, CA.