A phase I trial for the treatment of purine analog-refractory chronic lymphocytic leukemia using autologous T cells genetically targeted to the B cell specific antigen CD19

[Guest guest]

Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting

Edition).

Vol 26, No 15S (May 20 Supplement), 2008: 3045

A phase I trial for the treatment of purine analog-refractory chronic

lymphocytic leukemia using autologous T cells genetically targeted to the B cell

specific antigen CD19

R. J. Brentjens, D. Hollyman, M. Weiss, J. Stefanski, M. Przybylowski, S.

Bartido, O. Borquez-Ojeda, C. , M. Heaney, I. Riviere and M. Sadelain

Memorial Sloan-Kettering Cancer Center, New York, NY

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.

Abstract presentation from the 2008 ASCO Annual Meeting