Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study

Carolina Colli Cruz(Baylor College of Medicine), Kenneth Micklethwaite(Baylor College of Medicine), Barbara Savoldo(Baylor College of Medicine), Carlos A. Ramos(Baylor College of Medicine), Sharon Lam(Baylor College of Medicine), Stephanie Ku(Baylor College of Medicine), Oumar Diouf(Baylor College of Medicine), Enli Liu(Baylor College of Medicine), A. John Barrett(National Institutes of Health), Sawa Ito(National Institutes of Health), Elizabeth J. Shpall(The University of Texas MD Anderson Cancer Center), Robert A. Krance(Baylor College of Medicine), Rammurti T. Kamble(Baylor College of Medicine), George Carrum(Baylor College of Medicine), Chitra Hosing(The University of Texas MD Anderson Cancer Center), Adrian P. Gee(Baylor College of Medicine), Zhuyong Mei(Baylor College of Medicine), Bambi Grilley(Baylor College of Medicine), Helen E. Heslop(Baylor College of Medicine), Cliona M. Rooney(Baylor College of Medicine), Malcolm K. Brenner(Baylor College of Medicine), Catherine M. Bollard(Baylor College of Medicine), Gianpietro Dotti(Baylor College of Medicine)
Blood
September 13, 2013
10.1182/blood-2013-06-506741
Cited by 504Open Access
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Abstract

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

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