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Yeast PP4 Interacts with ATR Homolog Ddc2-Mec1 and Regulates Checkpoint Signaling

Robbins, PF and Kassim, SH and Tran, TL and Crystal, JS and Morgan, RA and Feldman, SA and Yang, JC and Dudly, ME and Wunderlich, JR and Sherry, RM and Kammula, US and Hughes, MS and Restifo, NP and Raffeld, M and Lee, CR and Li, YF and El-Gamil, M and Rosenberg, SA (2014) Yeast PP4 Interacts with ATR Homolog Ddc2-Mec1 and Regulates Checkpoint Signaling. Clinical Cancer Research.

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 70-80% and in approximately 25% of patients with synovial cell sarcoma and melanoma, respectively, prompted us to perform this first-in-man clinical trial employing the adoptive transfer of autologous PBMC that were retrovirally transduced with an NY-ESO-1 reactive 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 positive melanomas (55%) who received autologous T cells transduced with an NY-ESO-1-reactive TCR demonstrated objective clinical responses. The estimated overall three and five year survival rates for patients with synovial cell sarcoma were 38 and 14%, respectively, while the corresponding estimated survival rates for patients with melanoma were both 33%. Conclusions:

Item Type: Article
Additional Information: NIBR author: Dudly, ME institute: NIBR contributor address:
Date Deposited: 13 Oct 2015 13:11
Last Modified: 13 Oct 2015 13:11
URI: https://oak.novartis.com/id/eprint/24950

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