Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report
Background: Long-term follow-up on a clinical trial of 15 stage III-IV NSCLC patients treated with an Indoleamine 2,3-Dioxygenase (IDO) peptide vaccine (NCT01219348).Methods: Fifteen HLA-A2-positive patients with stable stage III-IV NSCLC after standard chemotherapy were treated with subcutaneous va...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02145/full |
| _version_ | 1818302711705108480 |
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| author | Julie Westerlin Kjeldsen Julie Westerlin Kjeldsen Trine Zeeberg Iversen Lotte Engell-Noerregaard Anders Mellemgaard Mads Hald Andersen Inge Marie Svane Inge Marie Svane |
| author_facet | Julie Westerlin Kjeldsen Julie Westerlin Kjeldsen Trine Zeeberg Iversen Lotte Engell-Noerregaard Anders Mellemgaard Mads Hald Andersen Inge Marie Svane Inge Marie Svane |
| author_sort | Julie Westerlin Kjeldsen |
| collection | DOAJ |
| description | Background: Long-term follow-up on a clinical trial of 15 stage III-IV NSCLC patients treated with an Indoleamine 2,3-Dioxygenase (IDO) peptide vaccine (NCT01219348).Methods: Fifteen HLA-A2-positive patients with stable stage III-IV NSCLC after standard chemotherapy were treated with subcutaneous vaccinations (100 μg IDO5 peptide, sequence ALLEIASCL, formulated in 900 μl Montanide) biweekly for 2.5 months and thereafter monthly until progression or up to 5 years. Here we report long-term clinical follow-up, toxicity and immunity.Results: Three of 15 patients are still alive corresponding to a 6-year overall survival of 20 %. Two patients continued monthly vaccinations for 5 years (56 vaccines). One of the two patients developed a partial response (PR) of target lesions in the liver 15 months after the first vaccine and has remained in PR ever since. The other patient had a solitary distant metastasis in a lymph node in retroperitoneum at baseline which normalized during treatment. All following evaluation scans during the treatment have been tumor free. The vaccine was well tolerated for all 5 years with no long-term toxicities registered. The third long-term surviving patient discontinued vaccinations after 11 months due to disease progression. Flow cytometry analyses of PBMCs from the two long-term responders demonstrated stable CD8+ and CD4+ T-cell populations during treatment. In addition, presence of IDO-specific T-cells was detected by IFN-γ Elispot in both patients at several time points during treatment.Conclusion: IDO peptide vaccination was well tolerated for administration up to 5years. Two of 15 patients are long-term responders with ongoing clinical response 6 years after 1st vaccination. |
| first_indexed | 2024-12-13T05:43:15Z |
| format | Article |
| id | doaj.art-9194c1a3d73946ebb83623ec0f556fca |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T05:43:15Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9194c1a3d73946ebb83623ec0f556fca2022-12-21T23:57:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02145411119Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research ReportJulie Westerlin Kjeldsen0Julie Westerlin Kjeldsen1Trine Zeeberg Iversen2Lotte Engell-Noerregaard3Anders Mellemgaard4Mads Hald Andersen5Inge Marie Svane6Inge Marie Svane7Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Hematology, Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Oncology, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Oncology, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Oncology, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Hematology, Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Oncology, Herlev Hospital, University of Copenhagen, Herlev, DenmarkDepartment of Hematology, Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, DenmarkBackground: Long-term follow-up on a clinical trial of 15 stage III-IV NSCLC patients treated with an Indoleamine 2,3-Dioxygenase (IDO) peptide vaccine (NCT01219348).Methods: Fifteen HLA-A2-positive patients with stable stage III-IV NSCLC after standard chemotherapy were treated with subcutaneous vaccinations (100 μg IDO5 peptide, sequence ALLEIASCL, formulated in 900 μl Montanide) biweekly for 2.5 months and thereafter monthly until progression or up to 5 years. Here we report long-term clinical follow-up, toxicity and immunity.Results: Three of 15 patients are still alive corresponding to a 6-year overall survival of 20 %. Two patients continued monthly vaccinations for 5 years (56 vaccines). One of the two patients developed a partial response (PR) of target lesions in the liver 15 months after the first vaccine and has remained in PR ever since. The other patient had a solitary distant metastasis in a lymph node in retroperitoneum at baseline which normalized during treatment. All following evaluation scans during the treatment have been tumor free. The vaccine was well tolerated for all 5 years with no long-term toxicities registered. The third long-term surviving patient discontinued vaccinations after 11 months due to disease progression. Flow cytometry analyses of PBMCs from the two long-term responders demonstrated stable CD8+ and CD4+ T-cell populations during treatment. In addition, presence of IDO-specific T-cells was detected by IFN-γ Elispot in both patients at several time points during treatment.Conclusion: IDO peptide vaccination was well tolerated for administration up to 5years. Two of 15 patients are long-term responders with ongoing clinical response 6 years after 1st vaccination.https://www.frontiersin.org/article/10.3389/fimmu.2018.02145/fullcancerimmunotherapyNSCLCIDOpeptide vaccine |
| spellingShingle | Julie Westerlin Kjeldsen Julie Westerlin Kjeldsen Trine Zeeberg Iversen Lotte Engell-Noerregaard Anders Mellemgaard Mads Hald Andersen Inge Marie Svane Inge Marie Svane Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report Frontiers in Immunology cancer immunotherapy NSCLC IDO peptide vaccine |
| title | Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report |
| title_full | Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report |
| title_fullStr | Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report |
| title_full_unstemmed | Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report |
| title_short | Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report |
| title_sort | durable clinical responses and long term follow up of stage iii iv non small cell lung cancer nsclc patients treated with ido peptide vaccine in a phase i study a brief research report |
| topic | cancer immunotherapy NSCLC IDO peptide vaccine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02145/full |
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