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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

2021; Landes Bioscience; Volume: 10; Issue: 1 Linguagem: Inglês

10.1080/2162402x.2021.1975889

2162-402X

Uffe Klausen, Nicolai Grønne 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,

Immunotherapy and Immune Responses

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.