Dataset Information

Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses in Patients.

ABSTRACT: Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens. T cells recognizing MTA have been detected in cancer patients and can even lead to tumor regression. Designing MTA-specific vaccination strategies will have to take into account the adjuvant activity of DC subsets and the best formulation to elicit an effective immune response. We discuss the potential of human DCs to prime MTA-specific responses.

SUBMITTER: Balan S

PROVIDER: S-EPMC5520811 | biostudies-literature | 2017 Mar/Apr

REPOSITORIES: biostudies-literature

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Publications

Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses in Patients.

Balan Sreekumar S Finnigan John J Bhardwaj Nina N

Cancer journal (Sudbury, Mass.) 20170301 2

Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-sh ...[more]

PMID: 28410301

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Project description:For successful therapeutic interventions in cancer immunotherapy, strong antigen-specific immune responses are required. To this end, immunostimulating cues must be combined with antigens to simultaneously arrive at antigen-presenting cells and initiate cellular immune responses. Recently, imidazoquinolines have shown their vast potential as small molecular Toll-like receptor 7/8 (TLR7/8) agonists for immunostimulation when delivered by nanocarriers. At the same time, peptide antigens are promising antigen candidates but require combination with immune-stimulating adjuvants to boost their immunogenicity and exploit their full potential. Consequently, we herein present biodegradable polycarbonate nanogels as versatile delivery system for adjuvants within the particles' core as well as for peptide antigens by surface decoration. For that purpose, orthogonally addressable multifunctional polycarbonate block copolymers were synthesized, enabling adjuvant conjugation through reactive ester chemistry and peptide decoration by strain-promoted alkyne-azide cycloaddition (SPAAC). In preparation for SPAAC, CD4+-specific peptide sequences of the model protein antigen ovalbumin were equipped with DBCO-moieties by site-selective modification at their N-terminal cysteine. With their azide groups exposed on their surface, the adjuvant-loaded nanogels were then efficiently decorated with DBCO-functional CD4+-peptides by SPAAC. In vitro evaluation of the adjuvant-loaded peptide-decorated gels then confirmed their strong immunostimulating properties as well as their high biocompatibility. Despite their covalent conjugation, the CD4+-peptide-decorated nanogels led to maturation of primary antigen-presenting cells and the downstream priming of CD4+-T cells. Subsequently, the peptide-decorated nanogels loaded with TLR7/8 agonist were successfully processed by antigen-presenting cells, enabling potent immune responses for future application in antigen-specific cancer immunotherapy.

Dataset Information

Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses in Patients.

Publications

Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses in Patients.

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