An immunogenic first-in-human immune modulatory vaccine with PD-L1 and PD-L2 peptides is feasible and shows early signs of efficacy in follicular lymphoma

Uffe Klausen, Nicolai Grønne Dahlager Jørgensen, Jacob Handlos Grauslund, Shamaila Munir Ahmad, Anne Ortved Gang, Evelina Martinenaite, Stine Emilie Weis-Banke, Marie Fredslund Breinholt, Guy Wayne Novotny, Julie Westerlin Kjeldsen, Morten Orebo Holmström, Lone Bredo Pedersen, Christian Bjørn Poulsen, Per Boye Hansen, Özcan Met, Inge Marie Svane, Carsten Utoft Niemann, Lars Møller Pedersen, Mads Hald Andersen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Cells in the tumor microenvironment of Follicular lymphoma (FL) express checkpoint molecules such as programmed death ligands 1 and 2 (PD-L1 and PD-L2) and are suppressing anti-tumor immune activity. Stimulation of peripheral blood mononuclear cells (PBMC) with PD-L1 (IO103) or PD-L2 (IO120) peptides can activate specific T cells inducing anti-regulatory functions including cytotoxicity against PD-L1/PD-L2-expressing cells. In this study, we vaccinated eight FL patients with PD-L1 and PD-L2 peptides following treatment with standard chemotherapy. Patients experienced grade 1–2 injection site reaction (5/8) and mild flu-like symptoms (6/8). One patient experienced neutropenia and thrombocytopenia during pseudo-progression. Enzyme-linked immunospot detected vaccine-specific immune responses in PBMC from all patients, predominately toward PD-L1. The circulating immune composition was stable during treatment; however, we observed a reduction regulatory T cells, however, not significant. One patient achieved a complete remission during vaccination and two patients had pseudo-progression followed by long-term disease regression. Further examination of these early signs of clinical efficacy of the dual-epitope vaccine in a larger study is warranted.

OriginalsprogEngelsk
Artikelnummer1975889
TidsskriftOncoImmunology
Vol/bind10
Udgave nummer1
ISSN2162-4011
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The work was funded through a research agreement between IO Biotech ApS and the National Center for Cancer Immune Therapy (CCIT-DK), Herlev Hospital, Capital Region, Denmark; National Center for Cancer Immune Therapy, Herlev Hospital [Basic support from Center]; Region Hovedstaden [Research agreement between the capital region of Denmark and IO Biotech]. We would like to acknowledge the tremendous technical support from Merete Jonassen, Sandra Ullitz F?rch, Betina Saxild, Susanne Wendt, and Christina Gr?nh?j. We would also like to thank Eva Ehrnrooth and Mai-Britt Zocca for their help and good discussions. Further we greatly acknowledge the EuroMRD consortium and the work by Professor Christiane Pott, Kiel, for developing a validated MRD assays in FL and providing the plasmids and primer sequences for the MRD analyses.

Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

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