Critical Role of Autophagy in the Processing of Adenovirus Capsid-Incorporated Cancer-Specific Antigens

Autor: Marta M. Alonso, Andrew Dong, Juan Fueyo, Sarah R. Klein, Hong Jiang, Candelaria Gomez-Manzano, Joy Gumin, Mohammad B. Hossain, Xuejun Fan
Rok vydání: 2016
Předmět:
0301 basic medicine
Adenoviruses
Physiology
Adenoviridae Infections
viruses
lcsh:Medicine
Virus Replication
Pathology and Laboratory Medicine
medicine.disease_cause
Biochemistry
Epitope
Major Histocompatibility Complex
Epitopes
Mice
Spectrum Analysis Techniques
0302 clinical medicine
Animal Cells
Neoplasms
Immune Physiology
Medicine and Health Sciences
lcsh:Science
Oncolytic Virotherapy
Staining
Antigen Presentation
Innate Immune System
Immune System Proteins
Multidisciplinary
Cell Death
Cell Staining
Flow Cytometry
3. Good health
Oncolytic Viruses
Medical Microbiology
Cell Processes
Spectrophotometry
Viral Pathogens
030220 oncology & carcinogenesis
Viruses
Cytophotometry
Pathogens
Cellular Types
Research Article
Oncolytic adenovirus
Autophagic Cell Death
Immune Cells
Genetic Vectors
Immunology
Antigen presentation
Antigen-Presenting Cells
Biology
Research and Analysis Methods
Microbiology
Antibodies
Adenoviridae
03 medical and health sciences
Capsid
Antigen
Antigens
Neoplasm
Cell Line
Tumor
Autophagy
medicine
Animals
Humans
Antigen-presenting cell
Microbial Pathogens
Biology and life sciences
lcsh:R
Organisms
Proteins
Cell Biology
Virology
Oncolytic virus
Mice
Inbred C57BL
030104 developmental biology
Specimen Preparation and Treatment
Immune System
lcsh:Q
Capsid Proteins
Clinical Immunology
Cancer vaccine
Clinical Medicine
DNA viruses
HeLa Cells
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 4, p e0153814 (2016)
ISSN: 1932-6203
Popis: Adenoviruses are highly immunogenic and are being examined as potential vectors for immunotherapy. Infection by oncolytic adenovirus is followed by massive autophagy in cancer cells. Here, we hypothesize that autophagy regulates the processing of adenoviral proteins for antigen presentation. To test this hypothesis, we first examined the presentation of viral antigens by infected cells using an antibody cocktail of viral capsid proteins. We found that viral antigens were processed by JNK-mediated autophagy, and that autophagy was required for their presentation. Consistent with these results, splenocytes isolated from virus-immunized mice were activated by infected cells in an MHC II-dependent manner. We then hypothesize that this mechanism can be utilized to generate an efficient cancer vaccine. To this end, we constructed an oncolytic virus encompassing an EGFRvIII cancer-specific epitope in the adenoviral fiber. Infection of cancer cells with this fiber-modified adenovirus resulted in recognition of infected cancer cells by a specific anti-EGFRvIII antibody. However, inhibition of autophagy drastically decreased the capability of the specific antibody to detect the cancer-related epitope in infected cells. Our data suggest that combination of adenoviruses with autophagy inducers may enhance the processing and presentation of cancer-specific antigens incorporated into capsid proteins.
Databáze: OpenAIRE
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