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.

PD-l1 PD-l2 anti-regulatory T cells anti-tregs follicular lymphoma immune modulatory vaccine

Journal

Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526

Informations de publication

Date de publication:
2021
Historique:
medline: 25 9 2021
pubmed: 25 9 2021
entrez: 29 1 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 38283034
doi: 10.1080/2162402X.2021.1975889
pii: 1975889
pmc: PMC10813564
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1975889

Informations de copyright

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

Déclaration de conflit d'intérêts

No potential conflict of interest was reported by the author(s).

Auteurs

Uffe Klausen (U)

Dept. Of Hematology, Herlev Hospital, Herlev, Denmark.
Dept. Of Hematology, Rigshospitalet, Copenhagen, Denmark.
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Nicolai Grønne Dahlager Jørgensen (N)

Dept. Of Hematology, Herlev Hospital, Herlev, Denmark.
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.

Jacob Handlos Grauslund (JH)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Shamaila Munir Ahmad (S)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.

Anne Ortved Gang (AO)

Dept. Of Hematology, Rigshospitalet, Copenhagen, Denmark.

Evelina Martinenaite (E)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.

Stine Emilie Weis-Banke (SE)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.

Marie Fredslund Breinholt (MF)

Dept. Of Pathology, Herlev Hospital, Herlev, Denmark.

Guy Wayne Novotny (GW)

Dept. Of Hematology, Herlev Hospital, Herlev, Denmark.
Dept. Of Pathology, Herlev Hospital, Herlev, Denmark.

Julie Westerlin Kjeldsen (JW)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Morten Orebo Holmström (M)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Lone Bredo Pedersen (LB)

Dept. Of Hematology, Rigshospitalet, Copenhagen, Denmark.

Christian Bjørn Poulsen (CB)

Dept. Of Hematology, Zealand University Hospital, Roskilde, Rosklide, Denmark.

Per Boye Hansen (PB)

Dept. Of Hematology, Zealand University Hospital, Roskilde, Rosklide, Denmark.

Özcan Met (Ö)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.

Inge Marie Svane (IM)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Carsten Utoft Niemann (CU)

Dept. Of Hematology, Rigshospitalet, Copenhagen, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Lars Møller Pedersen (LM)

Dept. Of Hematology, Herlev Hospital, Herlev, Denmark.
Dept. Of Hematology, Rigshospitalet, Copenhagen, Denmark.
Dept. Of Hematology, Zealand University Hospital, Roskilde, Rosklide, Denmark.

Mads Hald Andersen (MH)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology Herlev Hospital, Herlev, Denmark.
Institute for Immunology and Microbiology, Copenhagen University, Copenhagen K, Denmark.

Classifications MeSH