Abstract
Abstract 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) wildtype and transgenic cytotoxic (CD8+) T cells against ES. Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide specific allorepertoire-derived (i.e. allorestricted) CD8+ T cells. Patient #1 received up to 4.8x105/kg body weight HLA-A*02:01- allorestricted donor derived wild type CD8+ T cells. Patient #2 received up to 8.2x106/kg HLA-A*02:01- donor derived and patient #3 up to 6x106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for 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: CHM1319-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. Citation Format: Uwe Thiel, Sebastian Schober, ingo Einspieler, Andreas Kirschner, David Schirmer, Thomas Grünewald, Irene Teichert-von Lüttichau, Guenther Richter, Poul Sorensen, Stefan Burdach. Ewing Sarcoma regression by Allo-MHC/Chm1 specific T cells without GVHD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3757. doi:10.1158/1538-7445.AM2017-3757
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