Abstract B38: Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells

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) wild-type 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 4.8 x 105/kg body weight HLA-A*02:0 allorestricted donor-derived wild type CD8+ T cells. Patient #2 received up to 8.2 x 106/kg HLA-A*02:01 donor-derived and patient #3 up to 6 x 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319). Findings: 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. Interpretation: HLA-A*02:01/antigen specific allorestricted T cells proliferate in vivo without causing GVHD. CHM1319 TCR transgenic T cells home to affected BM and are associated with partial disease regression. Funding: Wilhelm Sander-Stiftung (2006.109.1), Else Kröner-Stiftung (GR & SB; P31/08//A123/07), BMBF (GR, UT and SB, TranSarNet 01GM1104B; SB, PROVABES 01KT1311) and Cura Placida Children's Cancer Research Foundation. PHS is funded by the Excellenzinitiative at TUM/CCC Munich. Citation Format: Uwe Thiel, Sebastian J. Schober, Ingo Einspieler, Andreas Kirschner, David Schirmer, Katja Gall, Oxana Schmidt, Thomas G. P. Grunewald, Poul H. Sorensen, Guenther H. S. Richter, Irene Teichert von Luettichau, Dirk H. Busch, Stefan Burdach. Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B38.