A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response

Abstract

Purpose: Although adoptive cell therapy can be highly effective for the treatment of patients with melanoma, the application of this approach to the treatment of other solid tumors has been limited. The observation that the cancer germline (CG) antigen NY-ESO-1 is expressed in 70% to 80% and in approximately 25% of patients with synovial cell sarcoma and melanoma, respectively, prompted us to perform this first-in-man clinical trial using the adoptive transfer of autologous peripheral blood mononuclear cells that were retrovirally transduced with an NY-ESO-1-reactive T-cell receptor (TCR) to heavily pretreated patients bearing these metastatic cancers.

Experimental design: HLA-*0201 patients with metastatic synovial cell sarcoma or melanoma refractory to standard treatments and whose cancers expressed NY-ESO-1 received autologous TCR-transduced T cells following a lymphodepleting preparative chemotherapy. Response rates using Response Evaluation Criteria in Solid Tumors (RECIST), as well as immunologic correlates of response, are presented in this report.

Results: Eleven of 18 patients with NY-ESO-1(+) synovial cell sarcomas (61%) and 11 of 20 patients with NY-ESO-1(+) melanomas (55%) who received autologous T cells transduced with an NY-ESO-1-reactive TCR demonstrated objective clinical responses. The estimated overall 3- and 5-year survival rates for patients with synovial cell sarcoma were 38% and 14%, respectively, whereas the corresponding estimated survival rates for patients with melanoma were both 33%.

Conclusions: The adoptive transfer of autologous T cells transduced with a retrovirus encoding a TCR against an HLA-A*0201 restricted NY-ESO-1 epitope can be an effective therapy for some patients bearing synovial cell sarcomas and melanomas that are refractory to other treatments.

Conflict of interest statement

The authors have no potential conflicts of interest to disclose

©2014 American Association for Cancer Research.

Figures

Figure 1

Computed tomography scans demonstrating tumor regression. Radiologic studies were carried out before and after treatment with the NY-ESO-1 TCR-transduced T cells. Tumors are indicated by arrows. (A) Continuing regression of lung metastases and a large pelvic lesion in a patient with synovial cell sarcoma (#7), with a partial response that is ongoing 44 months following adoptive T cell transfer. (B) Regression of representative lung metastases in a patient with synovial cell sarcoma (#15), who is exhibiting an ongoing complete response 17 months following adoptive T cell transfer. Regression of multiple liver (C) and lung lesions (D) in a patient with melanoma (#29) with a complete response that is ongoing 54 months after treatment.

Figure 2

Kaplan-Meier curve of overall survival and progression-free survival. The overall and progression-free survival of heavily pretreated synovial cell sarcoma patients (A) and melanoma patients (B) in response to therapy with NY-ESO-1 TCR transduced T cells is presented.

Figure 3

Association between number and function of administered T cells and response to therapy. Comparisons between the total number of T cells (A), the number of NY-ESO-1 peptide reactive IFN-γ ELISPOTS (B), and the number of tumor reactive IFN-γ ELISPOTS (C) administered to synovial cell sarcoma and melanoma patients are displayed. The associations between the number of administered T cells (D), the number of IFN-γ ELISPOTS generated by T cells in response an NY-ESO-1 peptide-pulsed, HLA-A*0201+ EBV transformed LCL (E) or number of IFN-γ ELISPOTS generated by TCR transduced T cells in response to the NY-ESO-1+ and HLA-A*0201+ tumor cell line 624 mel (C) were evaluated in responding as well as non-responding patients using Mann-Whitney non-parametric analysis. Median values are indicated by horizontal bars.