Efficient targeting of NY-ESO-1 tumor antigen to human cDC1s by lymphotactin results in cross-presentation and antigen-specific T cell expansion.
Antigens, Neoplasm
/ administration & dosage
CD8-Positive T-Lymphocytes
/ immunology
Cancer Vaccines
/ administration & dosage
Cross-Priming
Dendritic Cells
/ immunology
Epitopes
/ immunology
Esophageal Neoplasms
/ immunology
Esophageal Squamous Cell Carcinoma
/ immunology
Humans
Lymphokines
/ administration & dosage
Male
Membrane Proteins
/ administration & dosage
Sialoglycoproteins
/ administration & dosage
dendritic cells
vaccination
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
accepted:
15
03
2022
entrez:
16
4
2022
pubmed:
17
4
2022
medline:
20
4
2022
Statut:
ppublish
Résumé
Type 1 conventional dendritic cells (cDC1s) are characterized by their ability to induce potent CD8 To explore tumor antigen delivery to human cDC1s, we used an engineered version of XCR1-binding lymphotactin (XCL1), XCL1(CC3). Site-specific sortase-mediated transpeptidation was performed to conjugate XCL1(CC3) to an analog of the HLA-A*02:01 epitope of the cancer testis antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1). While poor epitope solubility prevented isolation of stable XCL1-antigen conjugates, incorporation of a single polyethylene glycol (PEG) chain upstream of the epitope-containing peptide enabled generation of soluble XCL1(CC3)-antigen fusion constructs. Binding and chemotactic characteristics of the XCL1-antigen conjugate, as well as its ability to induce antigen-specific CD8 PEGylated XCL1(CC3)-antigen conjugates retained binding to XCR1, and induced cDC1 chemoattraction in vitro. The model epitope was efficiently cross-presented by human cDC1s to activate NY-ESO-1-specific CD8 Our results present a novel strategy for the generation of targeted vaccines fused to insoluble antigens. Moreover, our data emphasize the potential of targeting XCR1 at the surface of primary human cDC1s to induce potent CD8
Sections du résumé
BACKGROUND
Type 1 conventional dendritic cells (cDC1s) are characterized by their ability to induce potent CD8
METHODS
To explore tumor antigen delivery to human cDC1s, we used an engineered version of XCR1-binding lymphotactin (XCL1), XCL1(CC3). Site-specific sortase-mediated transpeptidation was performed to conjugate XCL1(CC3) to an analog of the HLA-A*02:01 epitope of the cancer testis antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1). While poor epitope solubility prevented isolation of stable XCL1-antigen conjugates, incorporation of a single polyethylene glycol (PEG) chain upstream of the epitope-containing peptide enabled generation of soluble XCL1(CC3)-antigen fusion constructs. Binding and chemotactic characteristics of the XCL1-antigen conjugate, as well as its ability to induce antigen-specific CD8
RESULTS
PEGylated XCL1(CC3)-antigen conjugates retained binding to XCR1, and induced cDC1 chemoattraction in vitro. The model epitope was efficiently cross-presented by human cDC1s to activate NY-ESO-1-specific CD8
CONCLUSION
Our results present a novel strategy for the generation of targeted vaccines fused to insoluble antigens. Moreover, our data emphasize the potential of targeting XCR1 at the surface of primary human cDC1s to induce potent CD8
Identifiants
pubmed: 35428705
pii: jitc-2021-004309
doi: 10.1136/jitc-2021-004309
pmc: PMC9014073
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
CTAG1B protein, human
0
Cancer Vaccines
0
Epitopes
0
Lymphokines
0
Membrane Proteins
0
Sialoglycoproteins
0
lymphotactin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: No, there are no competing interests.
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