Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine.

Mohsen, Mona O.; Vogel, Monique; Riether, Carsten; Muller, Julius; Salatino, Silvia; Ternette, Nicola; Gomes, Ariane C; Cabral-Miranda, Gustavo; El-Turabi, Aadil; Ruedl, Christiane; Kundig, Thomas M; Dermime, Said; Knuth, Alexander; Speiser, Daniel E; Bachmann, Martin F. (2019). Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine. Frontiers in immunology, 10, p. 1015. Frontiers Research Foundation 10.3389/fimmu.2019.01015

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Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are sufficient, and whether the addition of germline antigens would enhance the therapeutic efficacy. We developed and used a personalized cancer nano-vaccine platform based on virus-like particles loaded with toll-like receptor ligands. We generated three sets of multi-target vaccines (MTV) to immunize against the aggressive B16F10 murine melanoma: one set based on germline epitopes (GL-MTV) identified by immunopeptidomics, another set based on mutated epitopes (Mutated-MTV) predicted by whole exome sequencing and a last set combines both germline and mutated epitopes (Mix-MTV). Our results demonstrate that both germline and mutated epitopes induced protection but the best therapeutic effect was achieved with the combination of both. Our platform is based on Cu-free click chemistry used for peptide-VLP coupling, thus enabling bedside production of a personalized cancer vaccine, ready for clinical translation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

UniBE Contributor:

Mohsen, Mona Omar Mahmoud; Vogel, Monique; Riether, Carsten; Cabral de Miranda, Gustavo and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

31 Oct 2019 13:54

Last Modified:

03 Nov 2019 02:42

Publisher DOI:

10.3389/fimmu.2019.01015

PubMed ID:

31156619

Uncontrolled Keywords:

germline melanoma mutated neoantigen personalized vaccine virus-like particles

BORIS DOI:

10.7892/boris.134303

URI:

https://boris.unibe.ch/id/eprint/134303

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