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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-07-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359221107113 |
| _version_ | 1828267749865947136 |
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| author | Valentina Hoyos Spyridoula Vasileiou Manik Kuvalekar Ayumi Watanabe Ifigeneia Tzannou Yovana Velazquez Matthew French-Kim Wingchi Leung Suhasini Lulla Catherine Robertson Claudette Foreman Tao Wang Shaun Bulsara Natalia Lapteva Bambi Grilley Matthew Ellis Charles Kent Osborne Angela Coscio Julie Nangia Helen E. Heslop Cliona M. Rooney Juan F. Vera Premal Lulla Mothaffar Rimawi Ann M. Leen |
| author_facet | Valentina Hoyos Spyridoula Vasileiou Manik Kuvalekar Ayumi Watanabe Ifigeneia Tzannou Yovana Velazquez Matthew French-Kim Wingchi Leung Suhasini Lulla Catherine Robertson Claudette Foreman Tao Wang Shaun Bulsara Natalia Lapteva Bambi Grilley Matthew Ellis Charles Kent Osborne Angela Coscio Julie Nangia Helen E. Heslop Cliona M. Rooney Juan F. Vera Premal Lulla Mothaffar Rimawi Ann M. Leen |
| author_sort | Valentina Hoyos |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T05:08:39Z |
| format | Article |
| id | doaj.art-d2a1cea135ca47b2969fd4c6813e68ff |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-04-13T05:08:39Z |
| publishDate | 2022-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-d2a1cea135ca47b2969fd4c6813e68ff2022-12-22T03:01:06ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592022-07-011410.1177/17588359221107113Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancerValentina HoyosSpyridoula VasileiouManik KuvalekarAyumi WatanabeIfigeneia TzannouYovana VelazquezMatthew French-KimWingchi LeungSuhasini LullaCatherine RobertsonClaudette ForemanTao WangShaun BulsaraNatalia LaptevaBambi GrilleyMatthew EllisCharles Kent OsborneAngela CoscioJulie NangiaHelen E. HeslopCliona M. RooneyJuan F. VeraPremal LullaMothaffar RimawiAnn M. LeenPurpose: 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.https://doi.org/10.1177/17588359221107113 |
| spellingShingle | Valentina Hoyos Spyridoula Vasileiou Manik Kuvalekar Ayumi Watanabe Ifigeneia Tzannou Yovana Velazquez Matthew French-Kim Wingchi Leung Suhasini Lulla Catherine Robertson Claudette Foreman Tao Wang Shaun Bulsara Natalia Lapteva Bambi Grilley Matthew Ellis Charles Kent Osborne Angela Coscio Julie Nangia Helen E. Heslop Cliona M. Rooney Juan F. Vera Premal Lulla Mothaffar Rimawi Ann M. Leen Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer Therapeutic Advances in Medical Oncology |
| 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 |
| url | https://doi.org/10.1177/17588359221107113 |
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