Dataset Information

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study.

ABSTRACT:

Purpose

Tumor-associated antigen cytotoxic T cells (TAA-Ts) represent a new, potentially effective and nontoxic therapeutic approach for patients with relapsed or refractory solid tumors. In this first-in-human trial, we investigated the safety of administering TAA-Ts that target Wilms tumor gene 1, preferentially expressed antigen of melanoma, and survivin to patients with relapsed/refractory solid tumors.

Materials and methods

TAA-T products were generated from autologous peripheral blood and infused over three dose levels: 1, 2, and 4 × 10⁷ cells/m². Patients were eligible for up to eight infusions administered 4 to 7 weeks apart. We assessed dose limiting toxicity during the first 45 days after infusion. Disease response was determined within the context of a phase I trial.

Results

There were no dose-limiting toxicities. Of 15 evaluable patients, 11 (73%) with stable disease or better at day 45 postinfusion were defined as responders. Six responders remain without progression at a median of 13.9 months (range, 4.1 to 19.9 months) after initial TAA-Ts. Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival of 73% after TAA-T infusion compared with a 38% 6-month progression-free survival with prior therapy. Antigen spreading and a reduction in circulating tumor-associated antigens using digital droplet polymerase chain reaction was observed in patients after TAA-T infusion.

Conclusion

TAA-Ts safely induced disease stabilization, prolonged time to progression, and were associated with antigen spreading and a reduction in circulating tumor-associated antigen DNA levels in patients with relapsed/refractory solid tumors without lymphodepleting chemotherapy before infusion. TAA-Ts are a promising new treatment approach for patients with solid tumors.

SUBMITTER: Hont AB

PROVIDER: S-EPMC6804838 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study.

Hont Amy B AB Cruz C Russell CR Ulrey Robert R O'Brien Barbara B Stanojevic Maja M Datar Anushree A Albihani Shuroug S Saunders Devin D Hanajiri Ryo R Panchapakesan Karuna K Darko Sam S Banerjee Payal P Fortiz Maria Fernanda MF Hoq Fahmida F Lang Haili H Wang Yunfei Y Hanley Patrick J PJ Dome Jeffrey S JS Bollard Catherine M CM Meany Holly J HJ

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20190729 26

<h4>Purpose</h4>Tumor-associated antigen cytotoxic T cells (TAA-Ts) represent a new, potentially effective and nontoxic therapeutic approach for patients with relapsed or refractory solid tumors. In this first-in-human trial, we investigated the safety of administering TAA-Ts that target Wilms tumor gene 1, preferentially expressed antigen of melanoma, and survivin to patients with relapsed/refractory solid tumors.<h4>Materials and methods</h4>TAA-T products were generated from autologous periph ...[more]

PMID: 31356143

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Dataset Information

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study.

Purpose

Materials and methods

Results

Conclusion

Publications

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study.

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