Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine
Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) inhibits T-cell activation and promotes T-cell differentiation into regulatory T-cells. Moreover, IDO expression promotes resistance to immunotherapies targeting immune checkpoints such as the cytotoxic T lymphocyte antigen-4 (CTL...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Case Reports in Medicine |
| Online Access: | http://dx.doi.org/10.1155/2016/9639585 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850166067935051776 |
|---|---|
| author | Mouldy Sioud Marta Nyakas Stein Sæbøe-Larssen Anne Mobergslien Steinar Aamdal Gunnar Kvalheim |
| author_facet | Mouldy Sioud Marta Nyakas Stein Sæbøe-Larssen Anne Mobergslien Steinar Aamdal Gunnar Kvalheim |
| author_sort | Mouldy Sioud |
| collection | DOAJ |
| description | Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) inhibits T-cell activation and promotes T-cell differentiation into regulatory T-cells. Moreover, IDO expression promotes resistance to immunotherapies targeting immune checkpoints such as the cytotoxic T lymphocyte antigen-4 (CTLA-4). Here, a patient with metastatic melanoma pretreated with ipilimumab, an anti-CTLA-4 blocking antibody, was vaccinated with IDO-silenced DCs cotransfected with mRNA for survivin or hTERT tumour antigens. During vaccination, T-cell responses to survivin and hTERT tumour antigens were generated, and a certain degree of clinical benefit was achieved, with a significant reduction in lung, liver, and skin metastases, along with a better performance status. T-cell responses against MART-1 and NY-ESO-1 tumour antigens were also detected in the peripheral blood. The patient also mounted an antibody response to several melanoma proteins, indicating diversification of the antitumour immunity in this patient. The identification of such serum antibody-reacting proteins could facilitate the discovery of tumour neoantigens. |
| format | Article |
| id | doaj-art-e405f936753c43219f659d34e32ad15d |
| institution | OA Journals |
| issn | 1687-9627 1687-9635 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Medicine |
| spelling | doaj-art-e405f936753c43219f659d34e32ad15d2025-08-20T02:21:34ZengWileyCase Reports in Medicine1687-96271687-96352016-01-01201610.1155/2016/96395859639585Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell VaccineMouldy Sioud0Marta Nyakas1Stein Sæbøe-Larssen2Anne Mobergslien3Steinar Aamdal4Gunnar Kvalheim5Department of Immunology, Oslo University Hospital, Montebello, 0310 Oslo, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, NorwayDepartment of Cell Therapy, Oslo University Hospital, Montebello, 0310 Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Montebello, 0310 Oslo, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, NorwayDepartment of Cell Therapy, Oslo University Hospital, Montebello, 0310 Oslo, NorwayIndoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) inhibits T-cell activation and promotes T-cell differentiation into regulatory T-cells. Moreover, IDO expression promotes resistance to immunotherapies targeting immune checkpoints such as the cytotoxic T lymphocyte antigen-4 (CTLA-4). Here, a patient with metastatic melanoma pretreated with ipilimumab, an anti-CTLA-4 blocking antibody, was vaccinated with IDO-silenced DCs cotransfected with mRNA for survivin or hTERT tumour antigens. During vaccination, T-cell responses to survivin and hTERT tumour antigens were generated, and a certain degree of clinical benefit was achieved, with a significant reduction in lung, liver, and skin metastases, along with a better performance status. T-cell responses against MART-1 and NY-ESO-1 tumour antigens were also detected in the peripheral blood. The patient also mounted an antibody response to several melanoma proteins, indicating diversification of the antitumour immunity in this patient. The identification of such serum antibody-reacting proteins could facilitate the discovery of tumour neoantigens.http://dx.doi.org/10.1155/2016/9639585 |
| spellingShingle | Mouldy Sioud Marta Nyakas Stein Sæbøe-Larssen Anne Mobergslien Steinar Aamdal Gunnar Kvalheim Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine Case Reports in Medicine |
| title | Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine |
| title_full | Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine |
| title_fullStr | Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine |
| title_full_unstemmed | Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine |
| title_short | Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine |
| title_sort | diversification of antitumour immunity in a patient with metastatic melanoma treated with ipilimumab and an ido silenced dendritic cell vaccine |
| url | http://dx.doi.org/10.1155/2016/9639585 |
| work_keys_str_mv | AT mouldysioud diversificationofantitumourimmunityinapatientwithmetastaticmelanomatreatedwithipilimumabandanidosilenceddendriticcellvaccine AT martanyakas diversificationofantitumourimmunityinapatientwithmetastaticmelanomatreatedwithipilimumabandanidosilenceddendriticcellvaccine AT steinsæbøelarssen diversificationofantitumourimmunityinapatientwithmetastaticmelanomatreatedwithipilimumabandanidosilenceddendriticcellvaccine AT annemobergslien diversificationofantitumourimmunityinapatientwithmetastaticmelanomatreatedwithipilimumabandanidosilenceddendriticcellvaccine AT steinaraamdal diversificationofantitumourimmunityinapatientwithmetastaticmelanomatreatedwithipilimumabandanidosilenceddendriticcellvaccine AT gunnarkvalheim diversificationofantitumourimmunityinapatientwithmetastaticmelanomatreatedwithipilimumabandanidosilenceddendriticcellvaccine |