TY - JOUR

T1 - 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

AU - Klausen, Uffe

AU - Grønne Dahlager Jørgensen, Nicolai

AU - Grauslund, Jacob Handlos

AU - Munir Ahmad, Shamaila

AU - Gang, Anne Ortved

AU - Martinenaite, Evelina

AU - Weis-Banke, Stine Emilie

AU - Breinholt, Marie Fredslund

AU - Novotny, Guy Wayne

AU - Kjeldsen, Julie Westerlin

AU - Orebo Holmström, Morten

AU - Pedersen, Lone Bredo

AU - Poulsen, Christian Bjørn

AU - Hansen, Per Boye

AU - Met, Özcan

AU - Svane, Inge Marie

AU - Niemann, Carsten Utoft

AU - Pedersen, Lars Møller

AU - Andersen, Mads Hald

N1 - Publisher Copyright: © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - anti-regulatory T cells

KW - anti-tregs

KW - follicular lymphoma

KW - immune modulatory vaccine

KW - PD-l1

KW - PD-l2

U2 - 10.1080/2162402X.2021.1975889

DO - 10.1080/2162402X.2021.1975889

M3 - Journal article

AN - SCOPUS:85115686622

VL - 10

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 1

M1 - 1975889

ER -