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

Conrad Russell Y. Cruz, Kenneth P. Micklethwaite, Barbara Savoldo, Carlos A. Ramos, Sharon Lam, Stephanie Ku, Oumar Diouf, Enli Liu, A. John Barrett, Sawa Ito, Elizabeth J. Shpall, Robert A. Krance, Rammurti T. Kamble, George Carrum, Chitra M. Hosing, Adrian P. Gee, Zhuyong Mei, Bambi J. Grilley, Helen E. Heslop, Cliona M. RooneyMalcolm K. Brenner, Catherine M. Bollard, Gianpietro Dotti

Research output: Contribution to journalArticle

323 Scopus citations

Abstract

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, butitisunknown whether allogeneic CD19.CARTcells 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 werenoinfusion-relatedtoxicities. VSTs persistedforamedianof8weeksinbloodand up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapseddiseaseduring the periodofCD19.CAR-VST persistence, whereas2patientswho received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation,donor CD19.CAR-VSTsexpanded concomitantlywithVSTs. HenceCD19.CAR-VSTsdisplayantitumoractivityand,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 ishigher)or planned vaccination with viral antigens may enhance disease control.

Original languageEnglish (US)
Pages (from-to)2956-2973
Number of pages18
JournalBlood
Volume122
Issue number17
DOIs
StatePublished - Oct 24 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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