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Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer

PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering...

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Autores principales: Hoyos, Valentina, Vasileiou, Spyridoula, Kuvalekar, Manik, Watanabe, Ayumi, Tzannou, Ifigeneia, Velazquez, Yovana, French-Kim, Matthew, Leung, Wingchi, Lulla, Suhasini, Robertson, Catherine, Foreman, Claudette, Wang, Tao, Bulsara, Shaun, Lapteva, Natalia, Grilley, Bambi, Ellis, Matthew, Osborne, Charles Kent, Coscio, Angela, Nangia, Julie, Heslop, Helen E., Rooney, Cliona M., Vera, Juan F., Lulla, Premal, Rimawi, Mothaffar, Leen, Ann M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290161/
https://www.ncbi.nlm.nih.gov/pubmed/35860837
http://dx.doi.org/10.1177/17588359221107113
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author Hoyos, Valentina
Vasileiou, Spyridoula
Kuvalekar, Manik
Watanabe, Ayumi
Tzannou, Ifigeneia
Velazquez, Yovana
French-Kim, Matthew
Leung, Wingchi
Lulla, Suhasini
Robertson, Catherine
Foreman, Claudette
Wang, Tao
Bulsara, Shaun
Lapteva, Natalia
Grilley, Bambi
Ellis, Matthew
Osborne, Charles Kent
Coscio, Angela
Nangia, Julie
Heslop, Helen E.
Rooney, Cliona M.
Vera, Juan F.
Lulla, Premal
Rimawi, Mothaffar
Leen, Ann M.
author_facet Hoyos, Valentina
Vasileiou, Spyridoula
Kuvalekar, Manik
Watanabe, Ayumi
Tzannou, Ifigeneia
Velazquez, Yovana
French-Kim, Matthew
Leung, Wingchi
Lulla, Suhasini
Robertson, Catherine
Foreman, Claudette
Wang, Tao
Bulsara, Shaun
Lapteva, Natalia
Grilley, Bambi
Ellis, Matthew
Osborne, Charles Kent
Coscio, Angela
Nangia, Julie
Heslop, Helen E.
Rooney, Cliona M.
Vera, Juan F.
Lulla, Premal
Rimawi, Mothaffar
Leen, Ann M.
author_sort Hoyos, Valentina
collection PubMed
description PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC. MATERIALS AND METHODS: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 10(7)/m(2). Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy. RESULTS: All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion. CONCLUSION: MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC.
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spelling pubmed-92901612022-07-19 Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer Hoyos, Valentina Vasileiou, Spyridoula Kuvalekar, Manik Watanabe, Ayumi Tzannou, Ifigeneia Velazquez, Yovana French-Kim, Matthew Leung, Wingchi Lulla, Suhasini Robertson, Catherine Foreman, Claudette Wang, Tao Bulsara, Shaun Lapteva, Natalia Grilley, Bambi Ellis, Matthew Osborne, Charles Kent Coscio, Angela Nangia, Julie Heslop, Helen E. Rooney, Cliona M. Vera, Juan F. Lulla, Premal Rimawi, Mothaffar Leen, Ann M. Ther Adv Med Oncol Original Research PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC. MATERIALS AND METHODS: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 10(7)/m(2). Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy. RESULTS: All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion. CONCLUSION: MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC. SAGE Publications 2022-07-15 /pmc/articles/PMC9290161/ /pubmed/35860837 http://dx.doi.org/10.1177/17588359221107113 Text en © The Author(s), 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Hoyos, Valentina
Vasileiou, Spyridoula
Kuvalekar, Manik
Watanabe, Ayumi
Tzannou, Ifigeneia
Velazquez, Yovana
French-Kim, Matthew
Leung, Wingchi
Lulla, Suhasini
Robertson, Catherine
Foreman, Claudette
Wang, Tao
Bulsara, Shaun
Lapteva, Natalia
Grilley, Bambi
Ellis, Matthew
Osborne, Charles Kent
Coscio, Angela
Nangia, Julie
Heslop, Helen E.
Rooney, Cliona M.
Vera, Juan F.
Lulla, Premal
Rimawi, Mothaffar
Leen, Ann M.
Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer
title Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer
title_full Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer
title_fullStr Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer
title_full_unstemmed Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer
title_short Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer
title_sort multi-antigen-targeted t-cell therapy to treat patients with relapsed/refractory breast cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290161/
https://www.ncbi.nlm.nih.gov/pubmed/35860837
http://dx.doi.org/10.1177/17588359221107113
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