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Clin Cancer Res. 2017 Mar 1;23(5):1156-1166. doi: 10.1158/1078-0432.CCR-16-1365. Epub 2016 Aug 31.

Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial.

Author information

1
Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
2
Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
3
Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
4
Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China.
5
Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China. hanwdrsw69@yahoo.com.

Abstract

Purpose: Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma.Experimental Design: Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).Results: Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 107 CAR-positive T cell per kg (SD, 0.25; range, 1.1-2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.Conclusions: CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment. Clin Cancer Res; 23(5); 1156-66. ©2016 AACR.

PMID:
27582488
DOI:
10.1158/1078-0432.CCR-16-1365
[Indexed for MEDLINE]
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