CMV Targeted T-Cell Program (CMV-CTL)

CMV VIREMIA OR CMV DISEASE FOLLOWING ALLOHCT

CMV is a common infection among adults and like EBV, a significant number of T-cells in normal healthy individuals are dedicated to maintaining CMV viral control. For patients undergoing alloHCT, the resulting impairment in T-cell function may lead to CMV reactivation. Over the past two decades, both prophylactic and preemptive therapy have been used to prevent CMV disease in the post-alloHCT setting. In prophylactic therapy, immunocompromised patients are given antiviral drugs for several months after alloHCT. In preemptive therapy, patients are intensively monitored for CMV activity after alloHCT by sensitive laboratory methods, and short-term antiviral treatment is given only to those with significant viral counts, or CMV viremia, before symptoms and overt CMV disease occur. Although both strategies can be effective for prevention of overt CMV disease, they rely on available drugs, which have significant toxicities, including marrow toxicity for ganciclovir, valganciclovir and cidofovir, and renal toxicity for foscarnet and cidofovir. As a result, some patients experience intolerance to these therapies and may ultimately progress to overt, symptomatic CMV disease. In addition, failure of antiviral drugs may occur when treating CMV, leaving affected patients with limited therapeutic options.

MECHANISM OF ACTION

In healthy individuals, a key T-cell function is to control CMV that, like EBV, remains present in the body after initial infection. Immunocompromised patients often lack sufficient T-cells to combat the virus. The CMV-CTLs provide the immunocompromised patient with T-cells designed to recognize and target CMV-infected cells.

PUBLICATIONS AND ORAL PRESENTATIONS

Prockop SE, Hasan AN, Koehne G, Doubrovina E, Sauter CS, Barker JN, Baroudy K, Boulad F, Giralt G, Khalaf R, Kernan NA, Papadopoulos EB, Ponce DM, Scaradavou A, Suser S, Wasilewski G, and O’Reilly RJ. Third Party Donor Derived CMV Specific T Cells for the Treatment of Refractory CMV Viremia and Disease after Hematopoietic Stem Cell Transplant. Blood (ASH Annual Meeting Abstracts) 2014: Abstract 184. Presented on December 7th, 2014 at the American Society of Hematology Annual Meeting 2014. (Citation)

Hasan AN, Prockop SE, Koehne G, Doubrovina E, and O’Reilly RJ. Banked, GMP Grade Third Party T-Cell Lines Specific for CMVpp65 Epitopes Presented By Certain Prevalent HLA Alleles More Consistently Clear CMV Infections in a Genetically Heterogeneous Population of HSCT Recipients.Blood (ASH Annual Meeting Abstracts) 2014: Abstract 309. Presented on December 8th, 2014 at the American Society of Hematology Annual Meeting 2014. (Citation)

Gupta MP, Coombs P, Prockop SE, Hasan AA, Doubrovina E, O’Reilly RJ, Cohen SH, Park SS, Kiss S. Treatment of cytomegalovirus retinitis with cytomegalovirus-specific T-lymphocyte infusion.Ophthalmic Surg Lasers Imaging Retina. 2015 Jan;46(1):80-2. doi: 10.3928/23258160-20150101-14. (Citation)

Koehne G, Hasan A, Doubrovina E, Prockop S, Tyler E, Wasilewski G, O’Reilly RJ. Immunotherapy with Donor T- Cells Sensitized with Overlapping Pentadecapeptides for Treatment of Persistent CMV Infection or Viremia. Biol Blood Marrow Transplant. 2015 May 29. pii: S1083-8791(15)00372-9. doi: 10.1016/j.bbmt.2015.05.015. [Epub ahead of print] (Citation)

Prockop SE, Hasan AN, Doubrovina E, Castro-Malaspina HR, Barker JN, Dahi PB, Boulad F, Kernan NA, Koehne G, Sauter CS, Kiss S, Patel M, Suser S, O’Reilly RJ. Successful Treatment of Refractory CMV Chorioretinitis and Meningoencephalitis with Adoptive Transfer of Third Party CMVpp65 Specific T-Cell Lines. Abstract 3157 presented December 6, 2015 at the American Society of Hematology Annual Meeting 2015. (Citation)