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
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
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. / 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.
In: OncoImmunology, Vol. 10, No. 1, 1975889, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 -
ID: 281156288