期刊
ONCOIMMUNOLOGY
卷 6, 期 5, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1312239
关键词
Allorestricted T cells; adoptive transfer; Ewing sarcoma; immunotherapy; T cell receptor transgenic T cells
资金
- Wilhelm Sander-Stiftung [2006.109.1]
- Else Kroner-Fresenius-Stiftung [P31/08//A123/07]
- BMBF [01KT1311, 01GM1104B]
- Deutsche Kinderkrebsstiftung [DKS 2010.07]
- Cura Placida Children's Cancer Research Foundation
- grant from 'Verein zur Forderung von Wissenschaft und Forschung an der Medizinischen Fakultat der LMU Munchen'
- Daimler and Benz Foundation
- Reinhard Frank Foundation
- LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative
- Mehr LEBEN fur krebskranke Kinder - Bettina-Brau-Stiftung
- Fritz-Thyssen Foundation [FTF-40.15.0.030MN]
- Friedrich-Baur Foundation
- German Cancer Aid [DKH-111886, DKH-70112257]
Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02: 01/CHM1-specific allorestricted T cell receptor (TCR) wild-type and transgenic cytotoxic (CD8C) T cells against ES. Patients and Methods: Three refractory HLA-A2C ES patients were treated with HLA-A*02: 01/peptidespecific allorepertoire-derived (i. e., allorestricted) CD8C T cells. Patient # 1 received up to 4.8 x 10(5)/kg body weight HLA-A*02: 01(-) allorestricted donor-derived wild-type CD8(+) T cells. Patient # 2 received up to 8.2 x 10(6)/kg HLA-A*02: 01(-) donor-derived and patient # 3 up to 6 x 10(6)/kg autologous allorestricted TCR transgenic CD8C T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319). Results: HLA-A*02: 01/CHM1319-specific allorestricted CD8(+) T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft versus host disease (GvHD). Patients # 1 and # 3 showed slow progression, whereas patient # 2, while having BM involvement, showed partial metastatic regression associated with T cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks. Conclusions: CHM1(319)-TCR transgenic T cells home to affected BM and may cause partial disease regression. HLA-A*02: 01/antigen-specific allorestricted T cells proliferate in vivo without causing GvHD.
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