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Thiel, Uwe; Schober, Sebastian J.; Einspieler, Ingo; Kirschner, Andreas; Thiede, Melanie; Schirmer, David; Gall, Katja; Blaeschke, Franziska; Schmidt, Oxana; Jabar, Susanne; Ranft, Andreas; Rubio, Rebeca Alba; Dirksen, Uta; Grunewald, Thomas G. P.; Sorensen, Poul H.; Richter, Günther H. S.; Teichert von Lüttichau, Irene; Busch, Dirk H. and Burdach, Stefan E. G. (2017): Ewing sarcoma partial regression without GvHD by chondromodulin-I/HLA-A*02:01-specific allorestricted T cell receptor transgenic T cells. In: Oncoimmunology, Vol. 6, No. 5, e1312239

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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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