Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers
Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W.
The American Association for Cancer Research (AACR)
Published 2018
The American Association for Cancer Research (AACR)
Published 2018
| Publication Date: |
2018-03-16
|
|---|---|
| Publisher: |
The American Association for Cancer Research (AACR)
|
| Print ISSN: |
1078-0432
|
| Electronic ISSN: |
1557-3265
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398847790678016 |
|---|---|
| autor | Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. |
| beschreibung | Purpose: This study is an expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor–engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTC). Experimental Design: Patients with EGFR-positive (〉50%) advanced unresectable, relapsed/metastatic BTCs were enrolled. Well-produced CART-EGFR cells were infused in a manner of dose escalation after the conditioning treatment with nab-paclitaxel (100–250 mg/m 2 ) and cyclophosphamide (15–35 mg/kg). Results: A total of 19 patients (14 cholangiocarcinomas and 5 gallbladder carcinomas) received one to three cycles of CART-EGFR cell infusion (median CART cell dose, 2.65 x 10 6 /kg; range, 0.8–4.1 x 10 6 /kg) within 6 months. The CART-EGFR cell infusion was tolerated, but 3 patients suffered grade ≥3 acute fever/chill. Grade 1/2 target-mediated toxicities including mucosal/cutaneous toxicities and acute pulmonary edema and grade ≥3 lymphopenia and thrombocytopenia related to the conditioning treatment were observed. Of 17 evaluable patients, 1 achieved complete response and 10 achieved stable disease. The median progression-free survival was 4 months (range, 2.5–22 months) from the first cycle of treatment. Analysis of data indicated that the enrichment of central memory T cells (Tcm) in the infused CART-EGFR cells improved the clinical outcome. Conclusions: The CART-EGFR cell immunotherapy was a safe and active strategy for EGFR-positive advanced BTCs. The enrichment of Tcm in the infused CART-EGFR cells could predict clinical response. Clin Cancer Res; 24(6); 1277–86. ©2017 AACR . See related commentary by Kalos, p. 1246 |
| citation_standardnr | 6208023 |
| datenlieferant | ipn_articles |
| feed_id | 9363 |
| feed_publisher | The American Association for Cancer Research (AACR) |
| feed_publisher_url | http://www.aacr.org/ |
| insertion_date | 2018-03-16 |
| journaleissn | 1557-3265 |
| journalissn | 1078-0432 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Association for Cancer Research (AACR) |
| quelle | Clinical Cancer Research |
| relation | http://clincancerres.aacrjournals.org/cgi/content/short/24/6/1277?rss=1 |
| search_space | articles |
| shingle_author_1 | Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. |
| shingle_author_2 | Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. |
| shingle_author_3 | Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. |
| shingle_author_4 | Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. |
| shingle_catch_all_1 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers Purpose: This study is an expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor–engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTC). Experimental Design: Patients with EGFR-positive (>50%) advanced unresectable, relapsed/metastatic BTCs were enrolled. Well-produced CART-EGFR cells were infused in a manner of dose escalation after the conditioning treatment with nab-paclitaxel (100–250 mg/m 2 ) and cyclophosphamide (15–35 mg/kg). Results: A total of 19 patients (14 cholangiocarcinomas and 5 gallbladder carcinomas) received one to three cycles of CART-EGFR cell infusion (median CART cell dose, 2.65 x 10 6 /kg; range, 0.8–4.1 x 10 6 /kg) within 6 months. The CART-EGFR cell infusion was tolerated, but 3 patients suffered grade ≥3 acute fever/chill. Grade 1/2 target-mediated toxicities including mucosal/cutaneous toxicities and acute pulmonary edema and grade ≥3 lymphopenia and thrombocytopenia related to the conditioning treatment were observed. Of 17 evaluable patients, 1 achieved complete response and 10 achieved stable disease. The median progression-free survival was 4 months (range, 2.5–22 months) from the first cycle of treatment. Analysis of data indicated that the enrichment of central memory T cells (Tcm) in the infused CART-EGFR cells improved the clinical outcome. Conclusions: The CART-EGFR cell immunotherapy was a safe and active strategy for EGFR-positive advanced BTCs. The enrichment of Tcm in the infused CART-EGFR cells could predict clinical response. Clin Cancer Res; 24(6); 1277–86. ©2017 AACR . See related commentary by Kalos, p. 1246 Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_2 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers Purpose: This study is an expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor–engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTC). Experimental Design: Patients with EGFR-positive (>50%) advanced unresectable, relapsed/metastatic BTCs were enrolled. Well-produced CART-EGFR cells were infused in a manner of dose escalation after the conditioning treatment with nab-paclitaxel (100–250 mg/m 2 ) and cyclophosphamide (15–35 mg/kg). Results: A total of 19 patients (14 cholangiocarcinomas and 5 gallbladder carcinomas) received one to three cycles of CART-EGFR cell infusion (median CART cell dose, 2.65 x 10 6 /kg; range, 0.8–4.1 x 10 6 /kg) within 6 months. The CART-EGFR cell infusion was tolerated, but 3 patients suffered grade ≥3 acute fever/chill. Grade 1/2 target-mediated toxicities including mucosal/cutaneous toxicities and acute pulmonary edema and grade ≥3 lymphopenia and thrombocytopenia related to the conditioning treatment were observed. Of 17 evaluable patients, 1 achieved complete response and 10 achieved stable disease. The median progression-free survival was 4 months (range, 2.5–22 months) from the first cycle of treatment. Analysis of data indicated that the enrichment of central memory T cells (Tcm) in the infused CART-EGFR cells improved the clinical outcome. Conclusions: The CART-EGFR cell immunotherapy was a safe and active strategy for EGFR-positive advanced BTCs. The enrichment of Tcm in the infused CART-EGFR cells could predict clinical response. Clin Cancer Res; 24(6); 1277–86. ©2017 AACR . See related commentary by Kalos, p. 1246 Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_3 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers Purpose: This study is an expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor–engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTC). Experimental Design: Patients with EGFR-positive (>50%) advanced unresectable, relapsed/metastatic BTCs were enrolled. Well-produced CART-EGFR cells were infused in a manner of dose escalation after the conditioning treatment with nab-paclitaxel (100–250 mg/m 2 ) and cyclophosphamide (15–35 mg/kg). Results: A total of 19 patients (14 cholangiocarcinomas and 5 gallbladder carcinomas) received one to three cycles of CART-EGFR cell infusion (median CART cell dose, 2.65 x 10 6 /kg; range, 0.8–4.1 x 10 6 /kg) within 6 months. The CART-EGFR cell infusion was tolerated, but 3 patients suffered grade ≥3 acute fever/chill. Grade 1/2 target-mediated toxicities including mucosal/cutaneous toxicities and acute pulmonary edema and grade ≥3 lymphopenia and thrombocytopenia related to the conditioning treatment were observed. Of 17 evaluable patients, 1 achieved complete response and 10 achieved stable disease. The median progression-free survival was 4 months (range, 2.5–22 months) from the first cycle of treatment. Analysis of data indicated that the enrichment of central memory T cells (Tcm) in the infused CART-EGFR cells improved the clinical outcome. Conclusions: The CART-EGFR cell immunotherapy was a safe and active strategy for EGFR-positive advanced BTCs. The enrichment of Tcm in the infused CART-EGFR cells could predict clinical response. Clin Cancer Res; 24(6); 1277–86. ©2017 AACR . See related commentary by Kalos, p. 1246 Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_4 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers Purpose: This study is an expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor–engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTC). Experimental Design: Patients with EGFR-positive (>50%) advanced unresectable, relapsed/metastatic BTCs were enrolled. Well-produced CART-EGFR cells were infused in a manner of dose escalation after the conditioning treatment with nab-paclitaxel (100–250 mg/m 2 ) and cyclophosphamide (15–35 mg/kg). Results: A total of 19 patients (14 cholangiocarcinomas and 5 gallbladder carcinomas) received one to three cycles of CART-EGFR cell infusion (median CART cell dose, 2.65 x 10 6 /kg; range, 0.8–4.1 x 10 6 /kg) within 6 months. The CART-EGFR cell infusion was tolerated, but 3 patients suffered grade ≥3 acute fever/chill. Grade 1/2 target-mediated toxicities including mucosal/cutaneous toxicities and acute pulmonary edema and grade ≥3 lymphopenia and thrombocytopenia related to the conditioning treatment were observed. Of 17 evaluable patients, 1 achieved complete response and 10 achieved stable disease. The median progression-free survival was 4 months (range, 2.5–22 months) from the first cycle of treatment. Analysis of data indicated that the enrichment of central memory T cells (Tcm) in the infused CART-EGFR cells improved the clinical outcome. Conclusions: The CART-EGFR cell immunotherapy was a safe and active strategy for EGFR-positive advanced BTCs. The enrichment of Tcm in the infused CART-EGFR cells could predict clinical response. Clin Cancer Res; 24(6); 1277–86. ©2017 AACR . See related commentary by Kalos, p. 1246 Guo, Y., Feng, K., Liu, Y., Wu, Z., Dai, H., Yang, Q., Wang, Y., Jia, H., Han, W. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_title_1 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers |
| shingle_title_2 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers |
| shingle_title_3 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers |
| shingle_title_4 | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers |
| timestamp | 2025-06-30T23:33:35.037Z |
| titel | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers |
| titel_suche | Phase I Study of Chimeric Antigen Receptor-Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers |
| topic | WW-YZ |
| uid | ipn_articles_6208023 |