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

By P. Robbins, Sadik H. Kassim, Thai L. Tran, J. Crystal, R. Morgan, S. Feldman, Jie Yang, M. Dudley, J. Wunderlich, R. Sherry and 8 more. Clinical Cancer Research, 2014

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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. Clin Cancer Res; 21(5); 1019–27. ©2014 AACR.

Subfields: Genetics, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/a404ccf1a4192d5a8bb41f1e478110d89de8fde0

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In Genetics

1. C. June
2. B. Levine
3. Howard Y. Chang
4. B. Carreno
5. J. Kochenderfer
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In Immunology

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Citations in the corpus

• CRISPR-engineered T cells in patients with refractory cancer (2020, result): “The stable engraftment of our engineered T cells is notably different from previously reported trials with NY-ESO1 TCR–engineered T cells, inwhich the half-life of the cells in blood was ~1 week (11, 32, 33).”
• Therapeutic cancer vaccines. (2010, background): “In many phase I/II studies, these vaccines have shown clinical benefit, in particular extended overall or disease-free survival, while objective durable regressions of the type associated with targeted or immunomodulatory mAb therapy (2–6) or chimeric antigen receptor (CAR) (7–10) or adoptive T cell”
• Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy (2020, background): “Adoptive transfer methods are based on patientderived lymphocytes that are expanded, genetically modified, or activated ex vivo before being reinfused (Robbins et al., 2015; Lu et al., 2017).”