Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma
The adoptive transfer of naturally occurring T cells that recognize cancer neoantigens has led to durable tumor regressions in select patients with cancer. However, it remains unknown whether such T cells can be isolated from and used to treat patients with glioblastoma, a cancer that is refractory...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2021-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/7/e002882.full |
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| _version_ | 1850062474289610752 |
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| author | Steven A Rosenberg Paul Robbins Biman Paria Todd D Prickett Jared J Gartner Devikala Gurusamy Stephanie L Goff Vid Leko Gal Cafri Rami Yossef Victoria Hill |
| author_facet | Steven A Rosenberg Paul Robbins Biman Paria Todd D Prickett Jared J Gartner Devikala Gurusamy Stephanie L Goff Vid Leko Gal Cafri Rami Yossef Victoria Hill |
| author_sort | Steven A Rosenberg |
| collection | DOAJ |
| description | The adoptive transfer of naturally occurring T cells that recognize cancer neoantigens has led to durable tumor regressions in select patients with cancer. However, it remains unknown whether such T cells can be isolated from and used to treat patients with glioblastoma, a cancer that is refractory to currently available therapies. To answer this question, we stimulated patient blood-derived memory T cells in vitro using peptides and minigenes that represented point mutations unique to patients’ tumors (ie, candidate neoantigens) and then tested their ability to specifically recognize these mutations. In a cohort of five patients with glioblastoma, we found that circulating CD4+ memory T cells from one patient recognized a cancer neoantigen harboring a mutation in the EED gene (EEDH189N) that was unique to that patient’s tumor. This finding suggests that neoantigen-reactive T cells could indeed be isolated from patients with glioblastoma, thereby providing a rationale for further efforts to develop neoantigen-directed adoptive T cell therapy for this disease. |
| format | Article |
| id | doaj-art-d996d8bb72c542bf890895b0f8a8b016 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d996d8bb72c542bf890895b0f8a8b0162025-08-20T02:49:55ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-07-019710.1136/jitc-2021-002882Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastomaSteven A Rosenberg0Paul Robbins1Biman Paria2Todd D Prickett3Jared J Gartner4Devikala Gurusamy5Stephanie L Goff6Vid Leko7Gal Cafri8Rami Yossef9Victoria Hill10National Cancer Institute, Bethesda, MD, USASurgery Branch, National Cancer Institute, Bethesda, Maryland, USAProgram Coordination and Referral Branch, National Cancer Institute, Bethesda, Maryland, USASurgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USASurgery Branch, National Cancer Institute, Bethesda, Maryland, USASurgery Branch, National Cancer Institute, Bethesda, Maryland, USASurgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USASurgery Branch, National Cancer Institute, Bethesda, Maryland, USASheba Medical Center, Ramat Gan, IsraelSurgery Branch, National Cancer Institute, Bethesda, Maryland, USASurgery Branch, National Cancer Institute, Bethesda, Maryland, USAThe adoptive transfer of naturally occurring T cells that recognize cancer neoantigens has led to durable tumor regressions in select patients with cancer. However, it remains unknown whether such T cells can be isolated from and used to treat patients with glioblastoma, a cancer that is refractory to currently available therapies. To answer this question, we stimulated patient blood-derived memory T cells in vitro using peptides and minigenes that represented point mutations unique to patients’ tumors (ie, candidate neoantigens) and then tested their ability to specifically recognize these mutations. In a cohort of five patients with glioblastoma, we found that circulating CD4+ memory T cells from one patient recognized a cancer neoantigen harboring a mutation in the EED gene (EEDH189N) that was unique to that patient’s tumor. This finding suggests that neoantigen-reactive T cells could indeed be isolated from patients with glioblastoma, thereby providing a rationale for further efforts to develop neoantigen-directed adoptive T cell therapy for this disease.https://jitc.bmj.com/content/9/7/e002882.full |
| spellingShingle | Steven A Rosenberg Paul Robbins Biman Paria Todd D Prickett Jared J Gartner Devikala Gurusamy Stephanie L Goff Vid Leko Gal Cafri Rami Yossef Victoria Hill Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma Journal for ImmunoTherapy of Cancer |
| title | Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma |
| title_full | Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma |
| title_fullStr | Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma |
| title_full_unstemmed | Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma |
| title_short | Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma |
| title_sort | identification of neoantigen reactive t lymphocytes in the peripheral blood of a patient with glioblastoma |
| url | https://jitc.bmj.com/content/9/7/e002882.full |
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