Abstract
3045 Background: We have developed a novel immunotherapy strategy based on the genetic modification of patient T cells to recognize the B cell-specific cellular antigen CD19, expressed on B cell tumors, through the retroviral expression of a chimeric antigen receptor (CAR) specific for CD19 (19–28z). Methods: We have initiated a clinical trial utilizing 19–28z+ autologous T cells in patients with purine analog-refractory chronic lymphocytic leukemia (CLL) (IRB #06–138). Enrolled patients initially undergo a leukopheresis procedure in order to obtain T cells. T cells are isolated and activated using Dynabeads ClinExVivo CD3/CD28 magnetic beads. Activated T cells are subsequently transduced with the CD19 specific 19–28z CAR using cGMP gammaretroviral vector stocks generated in our facility, and expanded utilizing a WaveTM bioreactor platform-based rapid expansion protocol. To assess safety, patients enrolled in the first cohort of this trial received an infusion of the lowest planned dose of modified T cells alone, subsequent cohorts will receive infusions of 19–28z+ T cells at the lowest planned dose level following escalating doses of cyclophosphamide chemotherapy followed by escalating doses of T cells after cyclophosphamide. Results: Patients treated in the first cohort with the lowest modified T cell dose alone experienced grade 2 fevers and rigors during infusion but no dose limiting toxicities. Treated patients variably experienced decrease in lymph node size, decreased CD19+ B cell numbers in the peripheral blood, and a decreased dependence on red blood cell transfusions. Conclusions: Infusion of genetically modified T cells targeted to CD19 is well tolerated in patients with refractory CLL with objective evidence of anti-tumor responses. We plan to enroll patients on the second planned cohort of this trial wherein patients will receive prior lymphodepleting chemotherapy with cyclophosphamide. The trial presented here is both the first to utilize gene modified autologous T cells for the treatment of CLL, as well as the first to target CD19+ tumors utilizing a rapid T cell expansion protocol, which represents a promising and novel treatment approach for patients with B cell malignancies. No significant financial relationships to disclose.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.