Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer
The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expres...
Saved in:
| Published in: | Science China. Life sciences 2016-05, Vol.59 (5), p.468-479 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | eng |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| recordid |
cdi_proquest_miscellaneous_1802201990 |
|---|---|
| title |
Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer |
| format |
Article |
| creator |
Feng, Kaichao Guo, Yelei Dai, Hanren Wang, Yao Li, Xiang Jia, Hejin Han, Weidong |
| subjects |
Adult Aged Biomedical and Life Sciences Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - therapy Female Humans Immunotherapy Life Sciences Lung Neoplasms - metabolism Lung Neoplasms - pathology Lung Neoplasms - therapy Male Middle Aged Receptor, Epidermal Growth Factor - metabolism Receptors, Antigen, T-Cell - immunology Recurrence Research Paper T-Lymphocytes - cytology 修饰 免疫原性 复发 晚期 细胞因子受体 细胞治疗 表皮生长因子受体 非小细胞肺癌 |
| ispartof |
Science China. Life sciences, 2016-05, Vol.59 (5), p.468-479 |
| description |
The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC. |
| language |
eng |
| source |
Alma/SFX Local Collection |
| identifier |
ISSN: 1674-7305 |
| fulltext |
fulltext |
| issn |
1674-7305 1869-1889 |
| url |
http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-05-28T16%3A15%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chimeric%20antigen%20receptor-modified%20T%20cells%20for%20the%20immunotherapy%20of%20patients%20with%20EGFR-expressing%20advanced%20relapsed/refractory%20non-small%20cell%20lung%20cancer&rft.jtitle=Science%20China.%20Life%20sciences&rft.au=Feng,%20Kaichao&rft.date=2016-05-01&rft.volume=59&rft.issue=5&rft.spage=468&rft.epage=479&rft.pages=468-479&rft.issn=1674-7305&rft.eissn=1869-1889&rft_id=info:doi/10.1007/s11427-016-5023-8&rft_dat=%3Cproquest_cross%3E4057772041%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c475t-3c47ac8b1a9715861d0c8c942959144cd6bc6cf8b08aa5adf73158a679b8a94b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1789140136&rft_id=info:pmid/26968708&rft_cqvip_id=668723397 |
| container_title |
Science China. Life sciences |
| container_volume |
59 |
| container_issue |
5 |
| container_start_page |
468 |
| container_end_page |
479 |
| fullrecord |
<record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1802201990</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>668723397</cqvip_id><sourcerecordid>4057772041</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-3c47ac8b1a9715861d0c8c942959144cd6bc6cf8b08aa5adf73158a679b8a94b3</originalsourceid><addsrcrecordid>eNp9kc1q3DAUhUVpaEKSB-imiHaTjRrJsvWzLEOSBgKFkq6FLMszCrbkSHbTeZS-be50JqF0UW2uQN8554qD0HtGPzNK5WVhrK4koUyQhlacqDfohCmhCVNKv4W7kDWRnDbH6LyUBwqHc1pJ-Q4dV0ILJak6Qb9XmzD6HBy2cQ5rH3H2zk9zymRMXeiD7_A9dn4YCu5TxvPG4zCOS0xwy3ba4tTjyc7Bx7ngpzBv8NXN9Xfif03ZlxLiGtvup40OfLIf7FR8d5l9n62DjC2OKZIy2mH4k4GHBQRuh-czdNTbofjzwzxFP66v7ldfyd23m9vVlzviatnMhMOwTrXMaskaJVhHnXK6rnSjWV27TrROuF61VFnb2K6XHDArpG6V1XXLT9HF3nfK6XHxZTZjKLtlbPRpKYYpWlWUaU0B_fQP-pCWHGE7w6SCOMq4AIrtKZdTKfBXM-Uw2rw1jJpddWZfnYHqzK46o0Dz4eC8tKPvXhUvRQFQ7YECT3Ht81_R_3H9eNhkk-L6EXSvxgJsK8615M9iobFS</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><isCDI>true</isCDI><recordtype>article</recordtype><pqid>1789140136</pqid></control><display><type>article</type><title>Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer</title><source>Alma/SFX Local Collection</source><creator>Feng, Kaichao ; Guo, Yelei ; Dai, Hanren ; Wang, Yao ; Li, Xiang ; Jia, Hejin ; Han, Weidong</creator><creatorcontrib>Feng, Kaichao ; Guo, Yelei ; Dai, Hanren ; Wang, Yao ; Li, Xiang ; Jia, Hejin ; Han, Weidong</creatorcontrib><description>The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.</description><identifier>ISSN: 1674-7305</identifier><identifier>EISSN: 1869-1889</identifier><identifier>DOI: 10.1007/s11427-016-5023-8</identifier><identifier>PMID: 26968708</identifier><language>eng</language><publisher>Beijing: Science China Press</publisher><subject>Adult ; Aged ; Biomedical and Life Sciences ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - therapy ; Female ; Humans ; Immunotherapy ; Life Sciences ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Male ; Middle Aged ; Receptor, Epidermal Growth Factor - metabolism ; Receptors, Antigen, T-Cell - immunology ; Recurrence ; Research Paper ; T-Lymphocytes - cytology ; 修饰 ; 免疫原性 ; 复发 ; 晚期 ; 细胞因子受体 ; 细胞治疗 ; 表皮生长因子受体 ; 非小细胞肺癌</subject><ispartof>Science China. Life sciences, 2016-05, Vol.59 (5), p.468-479</ispartof><rights>The Author(s) 2016</rights><rights>Science in China Press and Springer-Verlag GmbH 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-3c47ac8b1a9715861d0c8c942959144cd6bc6cf8b08aa5adf73158a679b8a94b3</citedby><cites>FETCH-LOGICAL-c475t-3c47ac8b1a9715861d0c8c942959144cd6bc6cf8b08aa5adf73158a679b8a94b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/60112X/60112X.jpg</thumbnail><link.rule.ids>315,787,791,27985,27986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26968708$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Kaichao</creatorcontrib><creatorcontrib>Guo, Yelei</creatorcontrib><creatorcontrib>Dai, Hanren</creatorcontrib><creatorcontrib>Wang, Yao</creatorcontrib><creatorcontrib>Li, Xiang</creatorcontrib><creatorcontrib>Jia, Hejin</creatorcontrib><creatorcontrib>Han, Weidong</creatorcontrib><title>Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer</title><title>Science China. Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.</description><subject>Adult</subject><subject>Aged</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Life Sciences</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Recurrence</subject><subject>Research Paper</subject><subject>T-Lymphocytes - cytology</subject><subject>修饰</subject><subject>免疫原性</subject><subject>复发</subject><subject>晚期</subject><subject>细胞因子受体</subject><subject>细胞治疗</subject><subject>表皮生长因子受体</subject><subject>非小细胞肺癌</subject><issn>1674-7305</issn><issn>1869-1889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kc1q3DAUhUVpaEKSB-imiHaTjRrJsvWzLEOSBgKFkq6FLMszCrbkSHbTeZS-be50JqF0UW2uQN8554qD0HtGPzNK5WVhrK4koUyQhlacqDfohCmhCVNKv4W7kDWRnDbH6LyUBwqHc1pJ-Q4dV0ILJak6Qb9XmzD6HBy2cQ5rH3H2zk9zymRMXeiD7_A9dn4YCu5TxvPG4zCOS0xwy3ba4tTjyc7Bx7ngpzBv8NXN9Xfif03ZlxLiGtvup40OfLIf7FR8d5l9n62DjC2OKZIy2mH4k4GHBQRuh-czdNTbofjzwzxFP66v7ldfyd23m9vVlzviatnMhMOwTrXMaskaJVhHnXK6rnSjWV27TrROuF61VFnb2K6XHDArpG6V1XXLT9HF3nfK6XHxZTZjKLtlbPRpKYYpWlWUaU0B_fQP-pCWHGE7w6SCOMq4AIrtKZdTKfBXM-Uw2rw1jJpddWZfnYHqzK46o0Dz4eC8tKPvXhUvRQFQ7YECT3Ht81_R_3H9eNhkk-L6EXSvxgJsK8615M9iobFS</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Feng, Kaichao</creator><creator>Guo, Yelei</creator><creator>Dai, Hanren</creator><creator>Wang, Yao</creator><creator>Li, Xiang</creator><creator>Jia, Hejin</creator><creator>Han, Weidong</creator><general>Science China Press</general><general>Springer Nature B.V</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>~WA</scope><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0L</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7T5</scope></search><sort><creationdate>20160501</creationdate><title>Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer</title><author>Feng, Kaichao ; Guo, Yelei ; Dai, Hanren ; Wang, Yao ; Li, Xiang ; Jia, Hejin ; Han, Weidong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-3c47ac8b1a9715861d0c8c942959144cd6bc6cf8b08aa5adf73158a679b8a94b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Life Sciences</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Receptors, Antigen, T-Cell - immunology</topic><topic>Recurrence</topic><topic>Research Paper</topic><topic>T-Lymphocytes - cytology</topic><topic>修饰</topic><topic>免疫原性</topic><topic>复发</topic><topic>晚期</topic><topic>细胞因子受体</topic><topic>细胞治疗</topic><topic>表皮生长因子受体</topic><topic>非小细胞肺癌</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Kaichao</creatorcontrib><creatorcontrib>Guo, Yelei</creatorcontrib><creatorcontrib>Dai, Hanren</creatorcontrib><creatorcontrib>Wang, Yao</creatorcontrib><creatorcontrib>Li, Xiang</creatorcontrib><creatorcontrib>Jia, Hejin</creatorcontrib><creatorcontrib>Han, Weidong</creatorcontrib><collection>维普_期刊</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>维普中文期刊数据库</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Biology Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Immunology Abstracts</collection><jtitle>Science China. Life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Kaichao</au><au>Guo, Yelei</au><au>Dai, Hanren</au><au>Wang, Yao</au><au>Li, Xiang</au><au>Jia, Hejin</au><au>Han, Weidong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer</atitle><jtitle>Science China. Life sciences</jtitle><stitle>Sci. China Life Sci</stitle><addtitle>Sci China Life Sci</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>59</volume><issue>5</issue><spage>468</spage><epage>479</epage><pages>468-479</pages><issn>1674-7305</issn><eissn>1869-1889</eissn><notes>The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.</notes><notes>11-5841/Q</notes><notes>chimeric antigen receptor, immunotherapy, epidermal growth factor receptor, relapsed/refractory, non-small cell lungcancer</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>26968708</pmid><doi>10.1007/s11427-016-5023-8</doi><oa>free_for_read</oa></addata></record> |