EBV Targeted T-Cell Program (EBV-CTL)

EBV-PTLD FOLLOWING ALLOHCT AND SOT

In immunocompromised patients, EBV causes lymphomas and other lymphoproliferative disorders, collectively called EBV-PTLD. In clinical trials that enrolled patients with EBV-PTLD following HCT or SOT, efficacy following treatment with EBV-CTL compares favorably with historical data in these patient populations. In rituximab-refractory patients with EBV-PTLD after HCT, treatment with EBV-CTL resulted in one-year overall survival of approximately 60% in two separate clinical trials in comparison with historical data where median survival, or the time by which 50% of patients had died, was 16-56 days. In the setting of rituximab-refractory EBV-PTLD after SOT, similar results were observed, with one-year overall survival of approximately 60% in EBV-CTL-treated patients in comparison with an expected historical one-year survival of 36% in patients with high risk disease similar to the patients treated in the trials. In February 2015, the U.S. Food and Drug Administration, or the FDA, granted breakthrough therapy designation for EBV-CTL in the treatment of rituximab-refractory EBV-PTLD after HCT. Breakthrough therapy designation is an FDA process designed to accelerate the development and review of drugs intended to treat a serious condition when early trials show that the drug may be substantially better than current treatment.

MECHANISM OF ACTION

In normal individuals, a key T-cell function is ongoing suppression of EBV to maintain EBV viral latency. This virus is always present in the body after initial infection. Immunocompromised patients lack sufficient T-cells to control the virus. EBV-CTLs provide the immunocompromised patient with T-cells designed to recognize and target EBV-infected cells.

PUBLICATIONS AND ORAL PRESENTATIONS

Barker JN, Doubrovina E, Sauter C, Jaroscak JJ, Perales MA, Doubrovin M, Prockop SE, Koehne G and O’Reilly RJ. Successful treatment of EBV-associated post-transplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood. 2010; 116(23):5045-5049 (Citation)

Doubrovina E, Oflaz-Sozmen B, Prockop SE, Kernan NA, Abramson S, Teruya-Feldstein J, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012; 119(11):2644-56 (Citation)

Fox CP, Burns D, Parker AN, Peggs KS, Harvey CM, Natarajan S, et al.  EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplantation.2014; 49:280-6 (Citation)

Uhlin M, Wikell H, Sundin M, Blennow O, Maeurer M, Ringden O, et al.  Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation. Haematologica. 2014; 99(2):346-52. (Citation)

Prockop, S. et al. Epstein-Barr virus-specific cytotoxic T lymphocytes for treatment of rituximab-refractory Epstein-Barr virus-associated lymphoproliferative disorder. Abstract CT107. Presented on April 19th, 2015 at the American Association for Cancer Research Annual Meeting 2015, Philadelphia, PA. (Citation)

Prockop, S. et al. Banked EBV-specific T-cells from HLA-partially matched normal donors to induce durable remissions of rituximab refractory EBV+ B-cell lymphomas post hematopoietic and organ allografts. J Clin Oncol 33, 2015 (suppl; abstr 10016). Presented on June 1st, 2015 at the 2015 American Society of Clinical Oncology Annual Meeting 2015, Chicago, IL. (Citation)