Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial

Nicolai Grønne Jørgensen*, Uffe Klausen, Jacob Handlos Grauslund, Carsten Helleberg, Thomas Granum Aagaard, Trung Hieu Do, Shamaila Munir Ahmad, Lars Rønn Olsen, Tobias Wirenfeldt Klausen, Marie Fredslund Breinholt, Morten Hansen, Evelina Martinenaite, Özcan Met, Inge Marie Svane, Lene Meldgaard Knudsen, Mads Hald Andersen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

14 Downloads (Pure)

Abstract

Background: Immune checkpoint blockade with monoclonal antibodies targeting programmed death 1 (PD-1) and its ligand PD-L1 has played a major role in the rise of cancer immune therapy. We have identified naturally occurring self-reactive T cells specific to PD-L1 in both healthy donors and cancer patients. Stimulation with a PD-L1 peptide (IO103), activates these cells to exhibit inflammatory and anti-regulatory functions that include cytotoxicity against PD-L1–expressing target cells. This prompted the initiation of the present first-in-human study of vaccination with IO103, registered at clinicaltrials.org (NCT03042793).
Methods: Ten patients with multiple myeloma who were up to 6 months after high dose chemotherapy with autologous stem cell support, were enrolled. Subcutaneous vaccinations with IO103 with the adjuvant Montanide ISA 51 was given up to fifteen times during 1 year. Safety was assessed by the common toxicity criteria for adverse events (CTCAE). Immunogenicity of the vaccine was evaluated using IFNg enzyme linked immunospot and intracellular cytokine staining on blood and skin infiltrating lymphocytes from sites of delayed-type hypersensitivity. The clinical course was described.
Results: All adverse reactions to the PD-L1 vaccine were below CTCAE grade 3, and most were grade 1–2 injection site reactions. The total rate of adverse events was as expected for the population. All patients exhibited peptide specific immune responses in peripheral blood mononuclear cells and in skin-infiltrating lymphocytes after a delayedtype hypersensitivity test. The clinical course was as expected for the population. Three of 10 patients had improvements of responses which coincided with the vaccinations.
Conclusion: Vaccination against PD-L1 was associated with low toxicity and high immunogenicity. This study has prompted the initiation of later phase trials to assess the vaccines efficacy.
Clinical Trial Registration: clinicaltrials.org, identifier NCT03042793.
Original languageEnglish
Article number595035
JournalFrontiers in Immunology
Volume11
Number of pages11
ISSN1664-3224
DOIs
Publication statusPublished - 2020

Fingerprint Dive into the research topics of 'Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial'. Together they form a unique fingerprint.

Cite this