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

被引：440

作者：

Cruz, Conrad Russell Y. ^{[1
]}

Micklethwaite, Kenneth P. ^{[1
]}

Savoldo, Barbara ^{[1
]}

Ramos, Carlos A. ^{[1
]}

Lam, Sharon ^{[1
]}

Ku, Stephanie ^{[1
]}

Diouf, Oumar ^{[1
]}

Liu, Enli ^{[1
]}

Barrett, A. John ^{[2
]}

Ito, Sawa ^{[2
]}

Shpall, Elizabeth J. ^{[3
]}

Krance, Robert A. ^{[1
,4
]}

Kamble, Rammurti T. ^{[1
,4
]}

Carrum, George ^{[1
,4
]}

Hosing, Chitra M. ^{[3
]}

Gee, Adrian P. ^{[1
]}

Mei, Zhuyong ^{[1
]}

Grilley, Bambi J. ^{[1
]}

Heslop, Helen E. ^{[1
,4
]}

Rooney, Cliona M. ^{[1
]}

Brenner, Malcolm K. ^{[1
,4
]}

Bollard, Catherine M. ^{[1
,4
]}

Dotti, Gianpietro ^{[1
]}

机构：

[1] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[2] NHLBI, NIH, Bethesda, MD 20892 USA

[3] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[4] Methodist Hosp, Houston, TX 77030 USA

来源：

BLOOD | 2013年 / 122卷 / 17期

关键词：

CHIMERIC ANTIGEN RECEPTOR; ACUTE LYMPHOCYTIC-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; PERIPHERAL-BLOOD; LYMPHOMA; RECONSTITUTION; PERSISTENCE; INFECTION; RECIPIENTS;

D O I：

10.1182/blood-2013-06-506741

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cellmalignancies, but it is unknown whether allogeneic CD19.CART 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. This study is registered at clinicaltrials.gov as #NCT00840853.

引用

页码：2965 / 2973

页数：9

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