Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial
In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10 T cells per m after Flu (cohort A) or Flu/Cy...
Gespeichert in:
| Veröffentlicht in: | Nature cancer 2024-06, Vol.5 (6), p.880-894 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 894 |
|---|---|
| container_issue | 6 |
| container_start_page | 880 |
| container_title | Nature cancer |
| container_volume | 5 |
| creator | Hegde, Meenakshi Navai, Shoba DeRenzo, Christopher Joseph, Sujith K Sanber, Khaled Wu, Mengfen Gad, Ahmed Z Janeway, Katherine A Campbell, Matthew Mullikin, Dolores Nawas, Zeid Robertson, Catherine Mathew, Pretty R Zhang, Huimin Mehta, Birju Bhat, Raksha R Major, Angela Shree, Ankita Gerken, Claudia Kalra, Mamta Chakraborty, Rikhia Thakkar, Sachin G Dakhova, Olga Salsman, Vita S Grilley, Bambi Lapteva, Natalia Gee, Adrian Dotti, Gianpietro Bao, Riyue Salem, Ahmed Hamed Wang, Tao Brenner, Malcolm K Heslop, Helen E Wels, Winfried S Hicks, M John Gottschalk, Stephen Ahmed, Nabil |
| description | In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10
T cells per m
after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10
CAR
T cells per m
after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 . |
| doi_str_mv | 10.1038/s43018-024-00749-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3046512701</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3046512701</sourcerecordid><originalsourceid>FETCH-LOGICAL-c254t-33729c144a3b6ca54111fe8886f66fbaf0df03b233bbca6f115f36e650c8908d3</originalsourceid><addsrcrecordid>eNpNkE1LAzEYhIMottT-AQ-So5dovjfrrZRqhYJQ6jlms4ld2W3WZFfov3drq3h65zAzvPMAcE3wHcFM3SfOMFEIU44wzniO5BkYUykpIoxn5__0CExT-sAYU0GIyNUlGDElhcoyMQZvs74LdXgPfYLLxZqi1Dpb-crC-WwNN9C6uk7Q-M5FWO-bdhtK19auq8IO-hChKb_MzroSJhNtaMwDNLDdmuQggV2sTH0FLrypk5ue7gS8Pi428yVavTw9z2crZKngHWIso7klnBtWSGsEJ4R4p5SSXkpfGI9Lj1lBGSsKa6QflngmnRTYqhyrkk3A7bG3jeGzd6nTTZUO35udG8ZphrkUhGaYDFZ6tNoYUorO6zZWjYl7TbA-wNVHuHqAq3_gajmEbk79fdG48i_yi5J9A6mxc7w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3046512701</pqid></control><display><type>article</type><title>Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial</title><source>MEDLINE</source><source>Nature Journals Online</source><source>SpringerLink Journals - AutoHoldings</source><creator>Hegde, Meenakshi ; Navai, Shoba ; DeRenzo, Christopher ; Joseph, Sujith K ; Sanber, Khaled ; Wu, Mengfen ; Gad, Ahmed Z ; Janeway, Katherine A ; Campbell, Matthew ; Mullikin, Dolores ; Nawas, Zeid ; Robertson, Catherine ; Mathew, Pretty R ; Zhang, Huimin ; Mehta, Birju ; Bhat, Raksha R ; Major, Angela ; Shree, Ankita ; Gerken, Claudia ; Kalra, Mamta ; Chakraborty, Rikhia ; Thakkar, Sachin G ; Dakhova, Olga ; Salsman, Vita S ; Grilley, Bambi ; Lapteva, Natalia ; Gee, Adrian ; Dotti, Gianpietro ; Bao, Riyue ; Salem, Ahmed Hamed ; Wang, Tao ; Brenner, Malcolm K ; Heslop, Helen E ; Wels, Winfried S ; Hicks, M John ; Gottschalk, Stephen ; Ahmed, Nabil</creator><creatorcontrib>Hegde, Meenakshi ; Navai, Shoba ; DeRenzo, Christopher ; Joseph, Sujith K ; Sanber, Khaled ; Wu, Mengfen ; Gad, Ahmed Z ; Janeway, Katherine A ; Campbell, Matthew ; Mullikin, Dolores ; Nawas, Zeid ; Robertson, Catherine ; Mathew, Pretty R ; Zhang, Huimin ; Mehta, Birju ; Bhat, Raksha R ; Major, Angela ; Shree, Ankita ; Gerken, Claudia ; Kalra, Mamta ; Chakraborty, Rikhia ; Thakkar, Sachin G ; Dakhova, Olga ; Salsman, Vita S ; Grilley, Bambi ; Lapteva, Natalia ; Gee, Adrian ; Dotti, Gianpietro ; Bao, Riyue ; Salem, Ahmed Hamed ; Wang, Tao ; Brenner, Malcolm K ; Heslop, Helen E ; Wels, Winfried S ; Hicks, M John ; Gottschalk, Stephen ; Ahmed, Nabil</creatorcontrib><description>In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10
T cells per m
after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10
CAR
T cells per m
after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .</description><identifier>ISSN: 2662-1347</identifier><identifier>EISSN: 2662-1347</identifier><identifier>DOI: 10.1038/s43018-024-00749-6</identifier><identifier>PMID: 38658775</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Aged ; Cyclophosphamide - administration & dosage ; Cyclophosphamide - therapeutic use ; Female ; Humans ; Immunotherapy, Adoptive - adverse effects ; Immunotherapy, Adoptive - methods ; Lymphocyte Depletion - methods ; Male ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2 ; Receptors, Chimeric Antigen - immunology ; Sarcoma - immunology ; Sarcoma - therapy ; T-Lymphocytes - immunology ; Treatment Outcome ; Vidarabine - administration & dosage ; Vidarabine - analogs & derivatives ; Vidarabine - therapeutic use</subject><ispartof>Nature cancer, 2024-06, Vol.5 (6), p.880-894</ispartof><rights>2024. The Author(s), under exclusive licence to Springer Nature America, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c254t-33729c144a3b6ca54111fe8886f66fbaf0df03b233bbca6f115f36e650c8908d3</cites><orcidid>0000-0001-7049-7698 ; 0000-0001-9858-3643 ; 0000-0002-8927-9786 ; 0000-0003-3991-7468 ; 0000-0002-6149-3414 ; 0000-0003-1220-2788 ; 0000-0002-0982-8424 ; 0000-0002-6105-1704 ; 0000-0002-7778-7871 ; 0000-0001-6603-7664 ; 0000-0002-9261-1583 ; 0000-0003-1957-7160</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38658775$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hegde, Meenakshi</creatorcontrib><creatorcontrib>Navai, Shoba</creatorcontrib><creatorcontrib>DeRenzo, Christopher</creatorcontrib><creatorcontrib>Joseph, Sujith K</creatorcontrib><creatorcontrib>Sanber, Khaled</creatorcontrib><creatorcontrib>Wu, Mengfen</creatorcontrib><creatorcontrib>Gad, Ahmed Z</creatorcontrib><creatorcontrib>Janeway, Katherine A</creatorcontrib><creatorcontrib>Campbell, Matthew</creatorcontrib><creatorcontrib>Mullikin, Dolores</creatorcontrib><creatorcontrib>Nawas, Zeid</creatorcontrib><creatorcontrib>Robertson, Catherine</creatorcontrib><creatorcontrib>Mathew, Pretty R</creatorcontrib><creatorcontrib>Zhang, Huimin</creatorcontrib><creatorcontrib>Mehta, Birju</creatorcontrib><creatorcontrib>Bhat, Raksha R</creatorcontrib><creatorcontrib>Major, Angela</creatorcontrib><creatorcontrib>Shree, Ankita</creatorcontrib><creatorcontrib>Gerken, Claudia</creatorcontrib><creatorcontrib>Kalra, Mamta</creatorcontrib><creatorcontrib>Chakraborty, Rikhia</creatorcontrib><creatorcontrib>Thakkar, Sachin G</creatorcontrib><creatorcontrib>Dakhova, Olga</creatorcontrib><creatorcontrib>Salsman, Vita S</creatorcontrib><creatorcontrib>Grilley, Bambi</creatorcontrib><creatorcontrib>Lapteva, Natalia</creatorcontrib><creatorcontrib>Gee, Adrian</creatorcontrib><creatorcontrib>Dotti, Gianpietro</creatorcontrib><creatorcontrib>Bao, Riyue</creatorcontrib><creatorcontrib>Salem, Ahmed Hamed</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Brenner, Malcolm K</creatorcontrib><creatorcontrib>Heslop, Helen E</creatorcontrib><creatorcontrib>Wels, Winfried S</creatorcontrib><creatorcontrib>Hicks, M John</creatorcontrib><creatorcontrib>Gottschalk, Stephen</creatorcontrib><creatorcontrib>Ahmed, Nabil</creatorcontrib><title>Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial</title><title>Nature cancer</title><addtitle>Nat Cancer</addtitle><description>In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10
T cells per m
after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10
CAR
T cells per m
after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .</description><subject>Adult</subject><subject>Aged</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy, Adoptive - adverse effects</subject><subject>Immunotherapy, Adoptive - methods</subject><subject>Lymphocyte Depletion - methods</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Receptor, ErbB-2</subject><subject>Receptors, Chimeric Antigen - immunology</subject><subject>Sarcoma - immunology</subject><subject>Sarcoma - therapy</subject><subject>T-Lymphocytes - immunology</subject><subject>Treatment Outcome</subject><subject>Vidarabine - administration & dosage</subject><subject>Vidarabine - analogs & derivatives</subject><subject>Vidarabine - therapeutic use</subject><issn>2662-1347</issn><issn>2662-1347</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1LAzEYhIMottT-AQ-So5dovjfrrZRqhYJQ6jlms4ld2W3WZFfov3drq3h65zAzvPMAcE3wHcFM3SfOMFEIU44wzniO5BkYUykpIoxn5__0CExT-sAYU0GIyNUlGDElhcoyMQZvs74LdXgPfYLLxZqi1Dpb-crC-WwNN9C6uk7Q-M5FWO-bdhtK19auq8IO-hChKb_MzroSJhNtaMwDNLDdmuQggV2sTH0FLrypk5ue7gS8Pi428yVavTw9z2crZKngHWIso7klnBtWSGsEJ4R4p5SSXkpfGI9Lj1lBGSsKa6QflngmnRTYqhyrkk3A7bG3jeGzd6nTTZUO35udG8ZphrkUhGaYDFZ6tNoYUorO6zZWjYl7TbA-wNVHuHqAq3_gajmEbk79fdG48i_yi5J9A6mxc7w</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Hegde, Meenakshi</creator><creator>Navai, Shoba</creator><creator>DeRenzo, Christopher</creator><creator>Joseph, Sujith K</creator><creator>Sanber, Khaled</creator><creator>Wu, Mengfen</creator><creator>Gad, Ahmed Z</creator><creator>Janeway, Katherine A</creator><creator>Campbell, Matthew</creator><creator>Mullikin, Dolores</creator><creator>Nawas, Zeid</creator><creator>Robertson, Catherine</creator><creator>Mathew, Pretty R</creator><creator>Zhang, Huimin</creator><creator>Mehta, Birju</creator><creator>Bhat, Raksha R</creator><creator>Major, Angela</creator><creator>Shree, Ankita</creator><creator>Gerken, Claudia</creator><creator>Kalra, Mamta</creator><creator>Chakraborty, Rikhia</creator><creator>Thakkar, Sachin G</creator><creator>Dakhova, Olga</creator><creator>Salsman, Vita S</creator><creator>Grilley, Bambi</creator><creator>Lapteva, Natalia</creator><creator>Gee, Adrian</creator><creator>Dotti, Gianpietro</creator><creator>Bao, Riyue</creator><creator>Salem, Ahmed Hamed</creator><creator>Wang, Tao</creator><creator>Brenner, Malcolm K</creator><creator>Heslop, Helen E</creator><creator>Wels, Winfried S</creator><creator>Hicks, M John</creator><creator>Gottschalk, Stephen</creator><creator>Ahmed, Nabil</creator><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>7X8</scope><orcidid>https://orcid.org/0000-0001-7049-7698</orcidid><orcidid>https://orcid.org/0000-0001-9858-3643</orcidid><orcidid>https://orcid.org/0000-0002-8927-9786</orcidid><orcidid>https://orcid.org/0000-0003-3991-7468</orcidid><orcidid>https://orcid.org/0000-0002-6149-3414</orcidid><orcidid>https://orcid.org/0000-0003-1220-2788</orcidid><orcidid>https://orcid.org/0000-0002-0982-8424</orcidid><orcidid>https://orcid.org/0000-0002-6105-1704</orcidid><orcidid>https://orcid.org/0000-0002-7778-7871</orcidid><orcidid>https://orcid.org/0000-0001-6603-7664</orcidid><orcidid>https://orcid.org/0000-0002-9261-1583</orcidid><orcidid>https://orcid.org/0000-0003-1957-7160</orcidid></search><sort><creationdate>20240601</creationdate><title>Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial</title><author>Hegde, Meenakshi ; Navai, Shoba ; DeRenzo, Christopher ; Joseph, Sujith K ; Sanber, Khaled ; Wu, Mengfen ; Gad, Ahmed Z ; Janeway, Katherine A ; Campbell, Matthew ; Mullikin, Dolores ; Nawas, Zeid ; Robertson, Catherine ; Mathew, Pretty R ; Zhang, Huimin ; Mehta, Birju ; Bhat, Raksha R ; Major, Angela ; Shree, Ankita ; Gerken, Claudia ; Kalra, Mamta ; Chakraborty, Rikhia ; Thakkar, Sachin G ; Dakhova, Olga ; Salsman, Vita S ; Grilley, Bambi ; Lapteva, Natalia ; Gee, Adrian ; Dotti, Gianpietro ; Bao, Riyue ; Salem, Ahmed Hamed ; Wang, Tao ; Brenner, Malcolm K ; Heslop, Helen E ; Wels, Winfried S ; Hicks, M John ; Gottschalk, Stephen ; Ahmed, Nabil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c254t-33729c144a3b6ca54111fe8886f66fbaf0df03b233bbca6f115f36e650c8908d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy, Adoptive - adverse effects</topic><topic>Immunotherapy, Adoptive - methods</topic><topic>Lymphocyte Depletion - methods</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Receptor, ErbB-2</topic><topic>Receptors, Chimeric Antigen - immunology</topic><topic>Sarcoma - immunology</topic><topic>Sarcoma - therapy</topic><topic>T-Lymphocytes - immunology</topic><topic>Treatment Outcome</topic><topic>Vidarabine - administration & dosage</topic><topic>Vidarabine - analogs & derivatives</topic><topic>Vidarabine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hegde, Meenakshi</creatorcontrib><creatorcontrib>Navai, Shoba</creatorcontrib><creatorcontrib>DeRenzo, Christopher</creatorcontrib><creatorcontrib>Joseph, Sujith K</creatorcontrib><creatorcontrib>Sanber, Khaled</creatorcontrib><creatorcontrib>Wu, Mengfen</creatorcontrib><creatorcontrib>Gad, Ahmed Z</creatorcontrib><creatorcontrib>Janeway, Katherine A</creatorcontrib><creatorcontrib>Campbell, Matthew</creatorcontrib><creatorcontrib>Mullikin, Dolores</creatorcontrib><creatorcontrib>Nawas, Zeid</creatorcontrib><creatorcontrib>Robertson, Catherine</creatorcontrib><creatorcontrib>Mathew, Pretty R</creatorcontrib><creatorcontrib>Zhang, Huimin</creatorcontrib><creatorcontrib>Mehta, Birju</creatorcontrib><creatorcontrib>Bhat, Raksha R</creatorcontrib><creatorcontrib>Major, Angela</creatorcontrib><creatorcontrib>Shree, Ankita</creatorcontrib><creatorcontrib>Gerken, Claudia</creatorcontrib><creatorcontrib>Kalra, Mamta</creatorcontrib><creatorcontrib>Chakraborty, Rikhia</creatorcontrib><creatorcontrib>Thakkar, Sachin G</creatorcontrib><creatorcontrib>Dakhova, Olga</creatorcontrib><creatorcontrib>Salsman, Vita S</creatorcontrib><creatorcontrib>Grilley, Bambi</creatorcontrib><creatorcontrib>Lapteva, Natalia</creatorcontrib><creatorcontrib>Gee, Adrian</creatorcontrib><creatorcontrib>Dotti, Gianpietro</creatorcontrib><creatorcontrib>Bao, Riyue</creatorcontrib><creatorcontrib>Salem, Ahmed Hamed</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Brenner, Malcolm K</creatorcontrib><creatorcontrib>Heslop, Helen E</creatorcontrib><creatorcontrib>Wels, Winfried S</creatorcontrib><creatorcontrib>Hicks, M John</creatorcontrib><creatorcontrib>Gottschalk, Stephen</creatorcontrib><creatorcontrib>Ahmed, Nabil</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hegde, Meenakshi</au><au>Navai, Shoba</au><au>DeRenzo, Christopher</au><au>Joseph, Sujith K</au><au>Sanber, Khaled</au><au>Wu, Mengfen</au><au>Gad, Ahmed Z</au><au>Janeway, Katherine A</au><au>Campbell, Matthew</au><au>Mullikin, Dolores</au><au>Nawas, Zeid</au><au>Robertson, Catherine</au><au>Mathew, Pretty R</au><au>Zhang, Huimin</au><au>Mehta, Birju</au><au>Bhat, Raksha R</au><au>Major, Angela</au><au>Shree, Ankita</au><au>Gerken, Claudia</au><au>Kalra, Mamta</au><au>Chakraborty, Rikhia</au><au>Thakkar, Sachin G</au><au>Dakhova, Olga</au><au>Salsman, Vita S</au><au>Grilley, Bambi</au><au>Lapteva, Natalia</au><au>Gee, Adrian</au><au>Dotti, Gianpietro</au><au>Bao, Riyue</au><au>Salem, Ahmed Hamed</au><au>Wang, Tao</au><au>Brenner, Malcolm K</au><au>Heslop, Helen E</au><au>Wels, Winfried S</au><au>Hicks, M John</au><au>Gottschalk, Stephen</au><au>Ahmed, Nabil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial</atitle><jtitle>Nature cancer</jtitle><addtitle>Nat Cancer</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>5</volume><issue>6</issue><spage>880</spage><epage>894</epage><pages>880-894</pages><issn>2662-1347</issn><eissn>2662-1347</eissn><abstract>In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10
T cells per m
after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10
CAR
T cells per m
after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .</abstract><cop>England</cop><pmid>38658775</pmid><doi>10.1038/s43018-024-00749-6</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-7049-7698</orcidid><orcidid>https://orcid.org/0000-0001-9858-3643</orcidid><orcidid>https://orcid.org/0000-0002-8927-9786</orcidid><orcidid>https://orcid.org/0000-0003-3991-7468</orcidid><orcidid>https://orcid.org/0000-0002-6149-3414</orcidid><orcidid>https://orcid.org/0000-0003-1220-2788</orcidid><orcidid>https://orcid.org/0000-0002-0982-8424</orcidid><orcidid>https://orcid.org/0000-0002-6105-1704</orcidid><orcidid>https://orcid.org/0000-0002-7778-7871</orcidid><orcidid>https://orcid.org/0000-0001-6603-7664</orcidid><orcidid>https://orcid.org/0000-0002-9261-1583</orcidid><orcidid>https://orcid.org/0000-0003-1957-7160</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2662-1347 |
| ispartof | Nature cancer, 2024-06, Vol.5 (6), p.880-894 |
| issn | 2662-1347 2662-1347 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3046512701 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Adult Aged Cyclophosphamide - administration & dosage Cyclophosphamide - therapeutic use Female Humans Immunotherapy, Adoptive - adverse effects Immunotherapy, Adoptive - methods Lymphocyte Depletion - methods Male Middle Aged Prospective Studies Receptor, ErbB-2 Receptors, Chimeric Antigen - immunology Sarcoma - immunology Sarcoma - therapy T-Lymphocytes - immunology Treatment Outcome Vidarabine - administration & dosage Vidarabine - analogs & derivatives Vidarabine - therapeutic use |
| title | Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T18%3A06%3A44IST&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=Autologous%20HER2-specific%20CAR%20T%20cells%20after%20lymphodepletion%20for%20advanced%20sarcoma:%20a%20phase%201%20trial&rft.jtitle=Nature%20cancer&rft.au=Hegde,%20Meenakshi&rft.date=2024-06-01&rft.volume=5&rft.issue=6&rft.spage=880&rft.epage=894&rft.pages=880-894&rft.issn=2662-1347&rft.eissn=2662-1347&rft_id=info:doi/10.1038/s43018-024-00749-6&rft_dat=%3Cproquest_cross%3E3046512701%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3046512701&rft_id=info:pmid/38658775&rfr_iscdi=true |