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Biomimetic Glyconanoparticle Vaccine for Cancer Immunotherapy
- Source :
- ACS Nano, ACS Nano, American Chemical Society, 2019, 13 (3), pp.2936-2947. ⟨10.1021/acsnano.8b07241⟩, ACS Nano, 2019, 13 (3), pp.2936-2947. ⟨10.1021/acsnano.8b07241⟩, ACS nano, vol 13, iss 3
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- International audience; Cancer immunotherapy aims to harness the immune system to combat malignant processes. Transformed cells harbor diverse modifications that lead to formation of neoantigens, including aberrantly expressed cell surface carbohydrates. Targeting tumor-associated carbohydrate antigens (TACA) hold great potential for cancer immunotherapy. N-glycolylneuraminic acid (Neu5Gc) is a dietary non-human immunogenic carbohydrate that accumulates on human cancer cells, thereby generating neoantigens. In mice, passive immunotherapy with anti-Neu5Gc antibodies inhibits growth of Neu5Gc-positive tumors. Here, we designed an active cancer vaccine immunotherapy strategy to target Neu5Gc-positive tumors. We generated biomimetic glyconanoparticles using engineered αGal knockout porcine red blood cells to form nanoghosts (NGs) that either express (NG[pos]) or lack expression (NG[neg]) of Neu5Gc-glycoconjugates in their natural context. We demonstrated that optimized immunization of "human-like" Neu5Gc-deficient Cmah[−/−] mice with NG[pos] glyconanoparticles induce a strong, diverse and persistent anti-Neu5Gc IgG immune response. The resulting anti-Neu5Gc IgG antibodies were also detected within Neu5Gc-positive tumors and inhibited tumor growth in vivo. Using detailed glycan microarray analysis, we further demonstrate that the kinetics and quality of the immune responses influence the efficacy of the vaccine. These findings reinforce the potential of TACA neoantigens and the dietary non-human sialic acid Neu5Gc, in particular, as immunotherapy targets.
- Subjects :
- Swine
medicine.medical_treatment
General Physics and Astronomy
02 engineering and technology
01 natural sciences
Mice
Cancer immunotherapy
Biomimetic Materials
General Materials Science
Cancer
Mice, Knockout
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
biology
General Engineering
biomimetic
021001 nanoscience & nanotechnology
3. Good health
5.1 Pharmaceuticals
glycan microarray
sialic acid
Colonic Neoplasms
Immunotherapy
Development of treatments and therapeutic interventions
Antibody
0210 nano-technology
Biotechnology
N-glycolylneuraminic acid
Knockout
Context (language use)
Adenocarcinoma
010402 general chemistry
Cancer Vaccines
Article
Vaccine Related
Immune system
Antigen
medicine
Animals
Particle Size
Nanoscience & Nanotechnology
glyconanoparticle
Nutrition
cancer immunotherapy
Prevention
N-Acetylneuraminic Acid
neoantigen
0104 chemical sciences
Good Health and Well Being
Immunization
Cancer research
biology.protein
Nanoparticles
Neuraminic Acids
Cancer vaccine
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- Language :
- English
- ISSN :
- 19360851
- Database :
- OpenAIRE
- Journal :
- ACS Nano, ACS Nano, American Chemical Society, 2019, 13 (3), pp.2936-2947. ⟨10.1021/acsnano.8b07241⟩, ACS Nano, 2019, 13 (3), pp.2936-2947. ⟨10.1021/acsnano.8b07241⟩, ACS nano, vol 13, iss 3
- Accession number :
- edsair.doi.dedup.....4ad07446112d65009885548375ece98a