Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infil...

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Bibliographic Details
Published in:Cancers 2021-12, Vol.13 (23), p.6107
Main Authors: Hofer, Tamara, Rossi, Matteo, Carboni, Susanna, Di Berardino Besson, Wilma, von Laer, Dorothee, Wollmann, Guido, Derouazi, Madiha, Santiago-Raber, Marie-Laure
Format: Article
Language:English
Subjects:
Animal models
Antigen (tumor-associated)
Antigens
Antitumor activity
Bone marrow
Cancer
Cancer immunotherapy
Cancer vaccines
CD4 antigen
CD8 antigen
Cytokines
Cytotoxicity
Dendritic cells
Epitopes
Flow cytometry
Glycoproteins
Human papillomavirus
Immunotherapy
Infectious diseases
Inflammation
Lymph nodes
Lymphatic system
Lymphocytes T
Peptides
Phenotypes
Proteins
Software
Stomatitis
Tumor-infiltrating lymphocytes
Tumors
Vaccines
Viruses
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Summary:Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13236107