| Autor: |
Antoni Ribas, Arun Singh, Begoña Comin-Anduix, Bartosz Chmielowski, Siwen Hu-Lieskovan, Catherine S. Grasso, Alistair J. Cochran, Anusha Kalbasi, Ignacio Baselga Carretero, Ivan Perez Garcilazo, Mignonette Macabali, Jia Pang, Justin Tran, Paula Cabrera, Paula Kaplan-Lefko, Jennifer Tsoi, Xiaoyan Wang, Rong Rong Huang, Gardenia Cheung-Lau, Beata Berent-Maoz, Theodore S. Nowicki |
| Rok vydání: |
2023 |
| Popis: |
Purpose:Transgenic adoptive cell therapy (ACT) targeting the tumor antigen NY-ESO-1 can be effective for the treatment of sarcoma and melanoma. Preclinical models have shown that this therapy can be improved with the addition of dendritic cell (DC) vaccination and immune checkpoint blockade. We studied the safety, feasibility, and antitumor efficacy of transgenic ACT with DC vaccination, with and without CTLA-4 blockade with ipilimumab.Patients and Methods:Freshly prepared autologous NY-ESO-1–specific T-cell receptor (TCR) transgenic lymphocytes were adoptively transferred together with NY-ESO-1 peptide-pulsed DC vaccination in HLA-A2.1–positive subjects alone (ESO, NCT02070406) or with ipilimumab (INY, NCT01697527) in patients with advanced sarcoma or melanoma.Results:Six patients were enrolled in the ESO cohort, and four were enrolled in the INY cohort. Four out of six patients treated per ESO (66%), and two out of four patients treated per INY (50%) displayed evidence of tumor regression. Peripheral blood reconstitution with NY-ESO-1–specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsies via TCR sequencing. Multiparametric mass cytometry of transgenic cells demonstrated shifting of transgenic cells from memory phenotypes to more terminally differentiated effector phenotypes over time.Conclusions:ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipilimumab. Improvements are needed to maintain tumor responses. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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