Peptide Vaccination in Combination With Either Ipilimumab or Vemurafenib for the Treatment of Patients With Unresectable Stage III or IV Malignant Melanoma A Phase I Study (First in Man)

The purpose of the study is to assess whether a vaccine containing a small fragment of the protein IDO, which may be present in cancer cells and cells of the immune system, is safe to use in combination with either Ipilimumab or Vemurafenib in the treatment of malignant melanoma that has metastasized.

开始日期2014-02-01

申办/合作机构

Herlev Hospital

100 项与 IDO peptide vaccine (IO Biotech) 相关的临床结果

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100 项与 IDO peptide vaccine (IO Biotech) 相关的转化医学

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100 项与 IDO peptide vaccine (IO Biotech) 相关的专利（医药）

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项与 IDO peptide vaccine (IO Biotech) 相关的文献（医药）

2022-05-03·Cancer Immunology Research

IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status

Article

作者: Gaur, Pankaj ; Verma, Vivek ; Yang, Xingdong ; Pedersen, Ayako Wakatsuki ; Shobaki, Nour ; Gupta, Seema ; Ramlaoui, Zainab ; Mkrtichyan, Mikayel ; Zocca, Mai-Britt ; Andersen, Mads Hald ; Patil, Veerupaxagouda ; Nandre, Rahul ; Khleif, Samir N.

AbstractThe immunosuppressive tumor microenvironment (TME) does not allow generation and expansion of antitumor effector cells. One of the potent immunosuppressive factors present in the TME is the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme, produced mainly by cancer cells and suppressive immune cells of myeloid origin. In fact, IDO+ myeloid-derived suppressor cells (MDSC) and dendritic cells (DC) tend to be more suppressive than their IDO− counterparts. Hence, therapeutic approaches that would target the IDO+ cells in the TME, while sparing the antigen-presenting functions of IDO− myeloid populations, are needed. Using an IDO-specific peptide vaccine (IDO vaccine), we explored the possibility of generating effector cells against IDO and non-IDO tumor-derived antigens. For this, IDO-secreting (B16F10 melanoma) and non–IDO-secreting (TC-1) mouse tumor models were employed. We showed that the IDO vaccine significantly reduced tumor growth and enhanced survival of mice in both the tumor models, which associated with a robust induction of IDO-specific effector cells in the TME. The IDO vaccine significantly enhanced the antitumor efficacy of non-IDO tumor antigen–specific vaccines, leading to an increase in the number of total and antigen-specific activated CD8+ T cells (IFNγ+ and granzyme B+). Treatment with the IDO vaccine significantly reduced the numbers of IDO+ MDSCs and DCs, and immunosuppressive regulatory T cells in both tumor models, resulting in enhanced therapeutic ratios. Together, we showed that vaccination against IDO is a promising therapeutic option for both IDO-producing and non–IDO-producing tumors. The IDO vaccine selectively ablates the IDO+ compartment in the TME, leading to a significant enhancement of the immune responses against other tumor antigen–specific vaccines.

1997-01-01·Immunological Investigations3区 · 医学

Identification of Core B Cell Epitope in the Synthetic Peptide Inducing Cross-Inhibiting Antibodies to a Surface Protein Antigen ofStreptococcus Mutans

3区 · 医学

Article

作者: Hiroaki Takeuchi ; Tosiki Nisizawa ; Hirohisa Kato ; Hidenobu Senpuku ; Akira Noda

A surface protein antigen (PAc) of Streptococcus mutans, in particular, A-region of the molecule, has been considered as a possible target for the development of an effective anticaries vaccine. This region might be implicated in the induction of dental caries via interaction with salivary components. We have recently specified a unique peptide, TYEAALKQYEADL, as one of the minimum peptides that completely corresponds to the amino acid sequence of a part of the A-region. The unique peptide contains both T and B cell epitopes for the induction of cross-reacting antibodies to the PAc. In this study, we synthesized valine or glycine-substituted peptide analogs of this peptide and examined core B cell epitopes of this unique peptide by using ELISA inhibition assay. As a result, the core amino acid residues of -Y------Y---- for B cell recognition were found to likely be not only important amino acids stabilizing the structure, but also might be essential for induction of the cross-inhibiting antibodies against PAc. These results will hopefully provide us with useful information for the design of an effective anticaries peptide vaccine.

Frontiers in Immunology2区 · 医学

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

2区 · 医学

ArticleOA

作者: Svane, Inge Marie ; Iversen, Trine Zeeberg ; Mellemgaard, Anders ; Kjeldsen, Julie Westerlin ; Engell-Noerregaard, Lotte ; Andersen, Mads Hald

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.

100 项与 IDO peptide vaccine (IO Biotech) 相关的药物交易

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