Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. The capacity of CD4+ Vγ9Vδ2 T cells to kill cancer cells correlates with co-expression of CD56

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Immune check point inhibitors are associated with a spectrum of cardiac events in patients with cancer

    Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

  3. ABO blood types and sepsis mortality

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking antibody ipilimumab (ipi).

METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response.

RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded to high-dose parenteral corticosteroids but later relapsed while the patient was admitted to a local hospital, where he died after receiving suboptimal therapy. Vaccine-specific T-cell responses were detectable ex vivo in three patients. At first evaluation, five of the 10 treated patients were in stable disease, one of whom had an unconfirmed partial response.

CONCLUSIONS: Treatment with IDOlong synthetic peptide vaccine in combination with ipi was generally safe and without augmented toxicity. The vaccine induced readily detectable T-cell responses in a subset of patients. Treatment showed signs of clinical activity, although not exceeding efficacy of ipi alone. Results should be confirmed in a larger study.

OriginalsprogEngelsk
TidsskriftCytotherapy
Vol/bind18
Udgave nummer8
Sider (fra-til)1043-55
Antal sider13
ISSN1465-3249
DOI
StatusUdgivet - aug. 2016

ID: 49619170