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 × 10(5)/kg body weight HLA-A*02:01(-) allorestricted donor-derived wild-type CD8(+) T cells. Patient #2 received up to 8.2 × 10(6)/kg HLA-A*02:01(-) donor-derived and patient #3 up to 6 × 10(6)/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 (CHM1(319)). Results: HLA-A*02:01/CHM1(319)-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. CHM1(319) 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.