Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial
BackgroundArginase-1-producing cells inhibit T cell-mediated anti-tumor responses by reducing L-arginine levels in the tumor microenvironment. T cell-facilitated elimination of arginase-1-expressing cells could potentially restore L-arginine levels and improve anti-tumor responses. The activation of...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023023/full |
| _version_ | 1811182396078292992 |
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| author | Cathrine Lund Lorentzen Evelina Martinenaite Evelina Martinenaite Julie Westerlin Kjeldsen Rikke Boedker Holmstroem Sofie Kirial Mørk Ayako Wakatsuki Pedersen Eva Ehrnrooth Mads Hald Andersen Inge Marie Svane |
| author_facet | Cathrine Lund Lorentzen Evelina Martinenaite Evelina Martinenaite Julie Westerlin Kjeldsen Rikke Boedker Holmstroem Sofie Kirial Mørk Ayako Wakatsuki Pedersen Eva Ehrnrooth Mads Hald Andersen Inge Marie Svane |
| author_sort | Cathrine Lund Lorentzen |
| collection | DOAJ |
| description | BackgroundArginase-1-producing cells inhibit T cell-mediated anti-tumor responses by reducing L-arginine levels in the tumor microenvironment. T cell-facilitated elimination of arginase-1-expressing cells could potentially restore L-arginine levels and improve anti-tumor responses. The activation of arginase-1-specific T cells may convert the immunosuppressive tumor microenvironment and induce or strengthen local Th1 inflammation. In the current clinical study, we examined the safety and immunogenicity of arginase-1-based peptide vaccination.MethodsIn this clinical phase I trial, ten patients with treatment-refractory progressive solid tumors were treated. The patients received an arginase-1 peptide vaccine comprising three 20-mer peptides from the ARG1 immunological “hot spot” region in combination with the adjuvant Montanide ISA-51. The vaccines were administered subcutaneously every third week (maximum 16 vaccines). The primary endpoint was to evaluate safety assessed by Common Terminology Criteria for Adverse Events 4.0 and laboratory monitoring. Vaccine-specific immune responses were evaluated using enzyme-linked immune absorbent spot assays and intracellular cytokine staining on peripheral blood mononuclear cells. Clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors 1.1.ResultsThe vaccination was feasible, and no vaccine-related grade 3–4 adverse events were registered. Nine (90%) of ten patients exhibited peptide-specific immune responses in peripheral blood mononuclear cells. Six (86%) of the seven evaluable patients developed a reactive T cell response against at least one of the ARG1 peptides during treatment. A phenotypic classification revealed that arginase-1 vaccine-specific T cells were both CD4+ T cells and CD8+ T cells. Two (20%) of ten patients obtained stable disease for respectively four- and seven months on vaccination treatment.ConclusionThe peptide vaccine against arginase-1 was safe. Nine (90%) of ten patients had measurable peptide-specific responses in the periphery blood, and two (20%) of ten patients attained stable disease on protocol treatment.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03689192, identifier NCT03689192. |
| first_indexed | 2024-04-11T09:30:48Z |
| format | Article |
| id | doaj.art-0746d310421f4a54b6021f1392b47672 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T09:30:48Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0746d310421f4a54b6021f1392b476722022-12-22T04:31:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10230231023023Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trialCathrine Lund Lorentzen0Evelina Martinenaite1Evelina Martinenaite2Julie Westerlin Kjeldsen3Rikke Boedker Holmstroem4Sofie Kirial Mørk5Ayako Wakatsuki Pedersen6Eva Ehrnrooth7Mads Hald Andersen8Inge Marie Svane9National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkIO Biotech ApS, Copenhagen, DenmarkNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkIO Biotech ApS, Copenhagen, DenmarkIO Biotech ApS, Copenhagen, DenmarkNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkBackgroundArginase-1-producing cells inhibit T cell-mediated anti-tumor responses by reducing L-arginine levels in the tumor microenvironment. T cell-facilitated elimination of arginase-1-expressing cells could potentially restore L-arginine levels and improve anti-tumor responses. The activation of arginase-1-specific T cells may convert the immunosuppressive tumor microenvironment and induce or strengthen local Th1 inflammation. In the current clinical study, we examined the safety and immunogenicity of arginase-1-based peptide vaccination.MethodsIn this clinical phase I trial, ten patients with treatment-refractory progressive solid tumors were treated. The patients received an arginase-1 peptide vaccine comprising three 20-mer peptides from the ARG1 immunological “hot spot” region in combination with the adjuvant Montanide ISA-51. The vaccines were administered subcutaneously every third week (maximum 16 vaccines). The primary endpoint was to evaluate safety assessed by Common Terminology Criteria for Adverse Events 4.0 and laboratory monitoring. Vaccine-specific immune responses were evaluated using enzyme-linked immune absorbent spot assays and intracellular cytokine staining on peripheral blood mononuclear cells. Clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors 1.1.ResultsThe vaccination was feasible, and no vaccine-related grade 3–4 adverse events were registered. Nine (90%) of ten patients exhibited peptide-specific immune responses in peripheral blood mononuclear cells. Six (86%) of the seven evaluable patients developed a reactive T cell response against at least one of the ARG1 peptides during treatment. A phenotypic classification revealed that arginase-1 vaccine-specific T cells were both CD4+ T cells and CD8+ T cells. Two (20%) of ten patients obtained stable disease for respectively four- and seven months on vaccination treatment.ConclusionThe peptide vaccine against arginase-1 was safe. Nine (90%) of ten patients had measurable peptide-specific responses in the periphery blood, and two (20%) of ten patients attained stable disease on protocol treatment.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03689192, identifier NCT03689192.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023023/fullarginase-1peptidevaccinationsolid tumorsfirst-in-human |
| spellingShingle | Cathrine Lund Lorentzen Evelina Martinenaite Evelina Martinenaite Julie Westerlin Kjeldsen Rikke Boedker Holmstroem Sofie Kirial Mørk Ayako Wakatsuki Pedersen Eva Ehrnrooth Mads Hald Andersen Inge Marie Svane Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial Frontiers in Immunology arginase-1 peptide vaccination solid tumors first-in-human |
| title | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial |
| title_full | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial |
| title_fullStr | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial |
| title_full_unstemmed | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial |
| title_short | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial |
| title_sort | arginase 1 targeting peptide vaccine in patients with metastatic solid tumors a phase i trial |
| topic | arginase-1 peptide vaccination solid tumors first-in-human |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023023/full |
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