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. (1st January 2021)

• Record Type: Journal Article
• Authors: Klausen, Uffe; Grønne Dahlager Jørgensen, Nicolai; Grauslund, Jacob Handlos; Munir Ahmad, Shamaila; Gang, Anne Ortved; Martinenaite, Evelina; Weis-Banke, Stine Emilie; Breinholt, Marie Fredslund; Novotny, Guy Wayne; Kjeldsen, Julie Westerlin; Orebo Holmström, Morten; Pedersen, Lone Bredo; Poulsen, Christian Bjørn; Hansen, Per Boye; Met, Özcan; Svane, Inge Marie; Niemann, Carsten Utoft; Pedersen, Lars Møller; Andersen, Mads Hald
• Is Part Of: Oncoimmunology. Volume 10:Number 1(2021)
• Publication Date: 2021-01-01
• Subjects: PD-l1 -- PD-l2 -- immune modulatory vaccine -- anti-regulatory T cells -- anti-tregs -- follicular lymphoma; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2021.1975889
• Languages: English
• ISSNs: 2162-402X

Abstract

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.