TY - JOUR
T1 - Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma
T2 - A Phase I First-in-Human Trial
AU - Jørgensen, Nicolai Grønne
AU - Klausen, Uffe
AU - Grauslund, Jacob Handlos
AU - Helleberg, Carsten
AU - Aagaard, Thomas Granum
AU - Do, Trung Hieu
AU - Ahmad, Shamaila Munir
AU - Olsen, Lars Rønn
AU - Klausen, Tobias Wirenfeldt
AU - Breinholt, Marie Fredslund
AU - Hansen, Morten
AU - Martinenaite, Evelina
AU - Met, Özcan
AU - Svane, Inge Marie
AU - Knudsen, Lene Meldgaard
AU - Andersen, Mads Hald
N1 - Copyright © 2020 Jørgensen, Klausen, Grauslund, Helleberg, Aagaard, Do, Ahmad, Olsen, Klausen, Breinholt, Hansen, Martinenaite, Met, Svane, Knudsen and Andersen.
PY - 2020/11/9
Y1 - 2020/11/9
N2 - 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 IFNγ 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 delayed-type 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.
AB - 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 IFNγ 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 delayed-type 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.
KW - first-in-human
KW - myeloma
KW - PD-L1
KW - peptide
KW - vaccination
U2 - 10.3389/fimmu.2020.595035
DO - 10.3389/fimmu.2020.595035
M3 - Journal article
C2 - 33240282
VL - 11
SP - 595035
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
ER -