CD27 stimulation unveils the efficacy of linked class I/II peptide vaccines in poorly immunogenic tumors by orchestrating a coordinated CD4/CD8 T cell response.

Autor: Riccione KA; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., He LZ; Celldex Therapeutics, Hampton, NJ, USA., Fecci PE; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA., Norberg PK; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA., Suryadevara CM; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA., Swartz A; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA., Healy P; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA., Reap E; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA., Keler T; Celldex Therapeutics, Hampton, NJ, USA., Li QJ; Department of Immunology, Duke University School of Medicine, Durham, NC, USA., Congdon KL; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA., Sanchez-Perez L; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA., Sampson JH; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC.; The Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA.; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
Jazyk: angličtina
Zdroj: Oncoimmunology [Oncoimmunology] 2018 Sep 05; Vol. 7 (12), pp. e1502904. Date of Electronic Publication: 2018 Sep 05 (Print Publication: 2018).
DOI: 10.1080/2162402X.2018.1502904
Abstrakt: Despite their promise, tumor-specific peptide vaccines have limited efficacy. CD27 is a costimulatory molecule expressed on CD4 + and CD8 + T cells that is important in immune activation. Here we determine if a novel CD27 agonist antibody (αhCD27) can enhance the antitumor T cell response and efficacy of peptide vaccines. We evaluated the effects of αhCD27 on the immunogenicity and antitumor efficacy of whole protein, class I-restricted, and class II-restricted peptide vaccines using a transgenic mouse expressing human CD27. We found that αhCD27 preferentially enhances the CD8 + T cell response in the setting of vaccines comprised of linked class I and II ovalbumin epitopes (SIINFEKL and TEWTSSNVMEERKIKV, respectively) compared to a peptide vaccine comprised solely of SIINFEKL, resulting in the antitumor efficacy of adjuvant αhCD27 against intracranial B16.OVA tumors when combined with vaccines containing linked class I/II ovalbumin epitopes. Indeed, we demonstrate that this efficacy is both CD8- and CD4-dependent and αhCD27 activity on ovalbumin-specific CD4 + T cells is necessary for its adjuvant effect. Importantly for clinical translation, a linked universal CD4 + helper epitope (tetanus P30) was sufficient to instill the efficacy of SIINFEKL peptide combined with αhCD27, eliminating the need for a tumor-specific class II-restricted peptide. This approach unveiled the efficacy of a class I-restricted peptide vaccine derived from the tumor-associated Trp2 antigen in mice bearing intracranial B16 tumors. CD27 agonist antibodies combined with peptide vaccines containing linked tumor-specific CD8 + epitopes and tumor-specific or universal CD4 + epitopes enhance the efficacy of active cancer immunotherapy.
Databáze: MEDLINE
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