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Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial
Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in mu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873554/ https://www.ncbi.nlm.nih.gov/pubmed/36624315 http://dx.doi.org/10.1038/s41591-022-02128-z |
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author | Hong, David S. Van Tine, Brian A. Biswas, Swethajit McAlpine, Cheryl Johnson, Melissa L. Olszanski, Anthony J. Clarke, Jeffrey M. Araujo, Dejka Blumenschein, George R. Kebriaei, Partow Lin, Quan Tipping, Alex J. Sanderson, Joseph P. Wang, Ruoxi Trivedi, Trupti Annareddy, Thejo Bai, Jane Rafail, Stavros Sun, Amy Fernandes, Lilliam Navenot, Jean-Marc Bushman, Frederic D. Everett, John K. Karadeniz, Derin Broad, Robyn Isabelle, Martin Naidoo, Revashnee Bath, Natalie Betts, Gareth Wolchinsky, Zohar Batrakou, Dzmitry G. Van Winkle, Erin Elefant, Erica Ghobadi, Armin Cashen, Amanda Grand’Maison, Anne McCarthy, Philip Fracasso, Paula M. Norry, Elliot Williams, Dennis Druta, Mihaela Liebner, David A. Odunsi, Kunle Butler, Marcus O. |
author_facet | Hong, David S. Van Tine, Brian A. Biswas, Swethajit McAlpine, Cheryl Johnson, Melissa L. Olszanski, Anthony J. Clarke, Jeffrey M. Araujo, Dejka Blumenschein, George R. Kebriaei, Partow Lin, Quan Tipping, Alex J. Sanderson, Joseph P. Wang, Ruoxi Trivedi, Trupti Annareddy, Thejo Bai, Jane Rafail, Stavros Sun, Amy Fernandes, Lilliam Navenot, Jean-Marc Bushman, Frederic D. Everett, John K. Karadeniz, Derin Broad, Robyn Isabelle, Martin Naidoo, Revashnee Bath, Natalie Betts, Gareth Wolchinsky, Zohar Batrakou, Dzmitry G. Van Winkle, Erin Elefant, Erica Ghobadi, Armin Cashen, Amanda Grand’Maison, Anne McCarthy, Philip Fracasso, Paula M. Norry, Elliot Williams, Dennis Druta, Mihaela Liebner, David A. Odunsi, Kunle Butler, Marcus O. |
author_sort | Hong, David S. |
collection | PubMed |
description | Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer (NCT03132922). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit–risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies. |
format | Online Article Text |
id | pubmed-9873554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-98735542023-01-26 Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial Hong, David S. Van Tine, Brian A. Biswas, Swethajit McAlpine, Cheryl Johnson, Melissa L. Olszanski, Anthony J. Clarke, Jeffrey M. Araujo, Dejka Blumenschein, George R. Kebriaei, Partow Lin, Quan Tipping, Alex J. Sanderson, Joseph P. Wang, Ruoxi Trivedi, Trupti Annareddy, Thejo Bai, Jane Rafail, Stavros Sun, Amy Fernandes, Lilliam Navenot, Jean-Marc Bushman, Frederic D. Everett, John K. Karadeniz, Derin Broad, Robyn Isabelle, Martin Naidoo, Revashnee Bath, Natalie Betts, Gareth Wolchinsky, Zohar Batrakou, Dzmitry G. Van Winkle, Erin Elefant, Erica Ghobadi, Armin Cashen, Amanda Grand’Maison, Anne McCarthy, Philip Fracasso, Paula M. Norry, Elliot Williams, Dennis Druta, Mihaela Liebner, David A. Odunsi, Kunle Butler, Marcus O. Nat Med Article Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer (NCT03132922). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit–risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies. Nature Publishing Group US 2023-01-09 2023 /pmc/articles/PMC9873554/ /pubmed/36624315 http://dx.doi.org/10.1038/s41591-022-02128-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Hong, David S. Van Tine, Brian A. Biswas, Swethajit McAlpine, Cheryl Johnson, Melissa L. Olszanski, Anthony J. Clarke, Jeffrey M. Araujo, Dejka Blumenschein, George R. Kebriaei, Partow Lin, Quan Tipping, Alex J. Sanderson, Joseph P. Wang, Ruoxi Trivedi, Trupti Annareddy, Thejo Bai, Jane Rafail, Stavros Sun, Amy Fernandes, Lilliam Navenot, Jean-Marc Bushman, Frederic D. Everett, John K. Karadeniz, Derin Broad, Robyn Isabelle, Martin Naidoo, Revashnee Bath, Natalie Betts, Gareth Wolchinsky, Zohar Batrakou, Dzmitry G. Van Winkle, Erin Elefant, Erica Ghobadi, Armin Cashen, Amanda Grand’Maison, Anne McCarthy, Philip Fracasso, Paula M. Norry, Elliot Williams, Dennis Druta, Mihaela Liebner, David A. Odunsi, Kunle Butler, Marcus O. Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial |
title | Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial |
title_full | Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial |
title_fullStr | Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial |
title_full_unstemmed | Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial |
title_short | Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial |
title_sort | autologous t cell therapy for mage-a4(+) solid cancers in hla-a*02(+) patients: a phase 1 trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873554/ https://www.ncbi.nlm.nih.gov/pubmed/36624315 http://dx.doi.org/10.1038/s41591-022-02128-z |
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