Abstract 3757: Ewing Sarcoma regression by Allo-MHC/Chm1 specific T cells without GVHD

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

TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model

“…Hence, the focus of TCR-based adoptive T cell transfer in EwS has mainly been on addressing cancer/testis antigens and overexpressed tumor-associated antigens (15)(16)(17). In this context, our group identified and characterized several TCRs derived from the allorepertoire with antitumor activity in vitro and in vivo (18)(19)(20)(21). The most promising candidate TCR directed against a nonameric peptide from chrondromodulin-1 (CHM1 319 , CHM1, CNMD), a direct downstream target of EWS-FLI1 mediating metastasis is applied in this work (22).…”