Periodic Reporting for period 1 - TALL (Targeted Antigen deLivery to Langerin: molecular basis of recognition and its implication in antigen uptake, processing and presentation to T cells)
Okres sprawozdawczy: 2020-09-01 do 2023-06-30
The aim of the project was to improve vaccine delivery methods beyond traditional hypodermal needles due to their drawbacks such as pain, invasiveness, and disposal costs. The proposed solution involves using microneedle patches to deliver vaccines directly into the skin's epidermis, targeting immune cells like dendritic cells for a more effective response. The approach could revolutionize vaccination by making it less painful, easier to self-administer, and cost-effective for disposal. It also holds promise for cancer immunotherapy, enhancing immune responses against cancer cells. To accomplish this project the main objectives were, first, engineering an antigenic scaffold that combines a langerin-targeted glycomimetic ligand with a T cell-stimulating peptide. This scaffold is meant to trigger immune responses for vaccine development. Second, studying the process of antigen uptake, processing, and presentation to T cells. This includes testing specificity with other skin cell receptors, monitoring antigen uptake by Langerin-expressing cell lines, and evaluating T cell activation and proliferation. Third, developing a system for transcutaneous cancer vaccination, leveraging the advantages of this novel approach over traditional methods. This could provide insights into immune cell activation and the induction of T cell responses.
The research project focused on the design, synthesis, and biological evaluation of antigenic peptides targeted to the langerin receptor, with the aim of enhancing immune responses for various applications including skin-based vaccinations, cancer therapy, and prevention of graft rejection and autoimmune diseases. The project progressed through several work packages, each involving specific tasks.
Work Performed:
Design and Synthesis: Antigenic peptides and a glycomimetic targeting ligand were designed to interact with the langerin receptor. Peptides from Ovalbumin (OVA) were chosen as model antigens. The project also focused on creating a cleavable linker and the targeting ligand.
Synthesis Challenges: Challenges were faced during the synthesis of targeting glycopeptides due to coupling issues. Alternative strategies were explored to construct the glycopeptides.
Cell Culture Experiments: Cell culture experiments were conducted to study the interaction between liposomes carrying the targeting ligand and langerin-expressing cells. Successful antigen presentation onto MHC II complexes was observed, suggesting the potential of lipid-based nanoparticles to boost immune responses.
Main Results Achieved:
Peptides from OVA were successfully synthesized, though the targeting glycopeptides were not completed in the given time frame due to synthesis challenges.
Liposomes with the targeting ligand were found to interact with langerin-expressing cells, enhancing the presentation of antigenic peptides on MHC II complexes.
Final Period Overview:
Despite considerable effort, the synthesis of targeting glycopeptides was not fully accomplished within the project's timeline due to coupling issues. Alternative approaches were explored. The project duration was shortened due to logistical and budget adjustments.
Exploitation and Dissemination:
The researcher actively shared project progress and findings through various means, such as press releases, interviews, seminars, podcasts, and participation in Women in Science events. The project contributed to the researcher's skill development in immunology, drug delivery, and nanoparticle formulation, even though the desired glycopeptide constructs weren't achieved as planned.
Work Performed:
Design and Synthesis: Antigenic peptides and a glycomimetic targeting ligand were designed to interact with the langerin receptor. Peptides from Ovalbumin (OVA) were chosen as model antigens. The project also focused on creating a cleavable linker and the targeting ligand.
Synthesis Challenges: Challenges were faced during the synthesis of targeting glycopeptides due to coupling issues. Alternative strategies were explored to construct the glycopeptides.
Cell Culture Experiments: Cell culture experiments were conducted to study the interaction between liposomes carrying the targeting ligand and langerin-expressing cells. Successful antigen presentation onto MHC II complexes was observed, suggesting the potential of lipid-based nanoparticles to boost immune responses.
Main Results Achieved:
Peptides from OVA were successfully synthesized, though the targeting glycopeptides were not completed in the given time frame due to synthesis challenges.
Liposomes with the targeting ligand were found to interact with langerin-expressing cells, enhancing the presentation of antigenic peptides on MHC II complexes.
Final Period Overview:
Despite considerable effort, the synthesis of targeting glycopeptides was not fully accomplished within the project's timeline due to coupling issues. Alternative approaches were explored. The project duration was shortened due to logistical and budget adjustments.
Exploitation and Dissemination:
The researcher actively shared project progress and findings through various means, such as press releases, interviews, seminars, podcasts, and participation in Women in Science events. The project contributed to the researcher's skill development in immunology, drug delivery, and nanoparticle formulation, even though the desired glycopeptide constructs weren't achieved as planned.
Progress beyond the State of the Art:
The project aimed to advance immune response modulation and targeted peptide delivery by designing and synthesizing antigenic peptides for the langerin receptor. Successful synthesis of OVA-derived peptides and antigen presentation on MHC-I/II complexes through liposomes with the targeting ligand showcased progress. However, challenges in glycopeptide synthesis prevented complete construct achievement. The use of lipid-based nanoparticles to enhance immune responses represents innovation beyond current methods, providing insights into immune recognition improvement.
Expected Results until the End of the Project:
Anticipated outcomes included successfully synthesizing targeting glycopeptides and demonstrating their interaction with langerin-expressing cells. These outcomes would have highlighted glycopeptides' potential for better antigen presentation and immune responses. Additionally, the project aimed to advance understanding of immune interactions and modulation strategies, applicable in vaccination, cancer therapy, and organ transplantation.
Potential Impacts:
Socio-Economic Impact: Successful project completion could have substantial socio-economic effects. Enhanced immune responses via targeted peptide delivery might revolutionize vaccinations for more effective disease prevention. Lipid-based nanoparticles in cancer therapy could lead to better treatment and reduced side effects, improving public health and lowering healthcare costs.
Wider Societal Implications: The project addresses critical healthcare challenges in cancer therapy and immune modulation, potentially offering new treatments. The active dissemination of findings and engagement in events like International Women and Girls in Science Day promotes scientific awareness and inspires individuals, especially women, to pursue STEM careers.
The project aimed to advance immune response modulation and targeted peptide delivery by designing and synthesizing antigenic peptides for the langerin receptor. Successful synthesis of OVA-derived peptides and antigen presentation on MHC-I/II complexes through liposomes with the targeting ligand showcased progress. However, challenges in glycopeptide synthesis prevented complete construct achievement. The use of lipid-based nanoparticles to enhance immune responses represents innovation beyond current methods, providing insights into immune recognition improvement.
Expected Results until the End of the Project:
Anticipated outcomes included successfully synthesizing targeting glycopeptides and demonstrating their interaction with langerin-expressing cells. These outcomes would have highlighted glycopeptides' potential for better antigen presentation and immune responses. Additionally, the project aimed to advance understanding of immune interactions and modulation strategies, applicable in vaccination, cancer therapy, and organ transplantation.
Potential Impacts:
Socio-Economic Impact: Successful project completion could have substantial socio-economic effects. Enhanced immune responses via targeted peptide delivery might revolutionize vaccinations for more effective disease prevention. Lipid-based nanoparticles in cancer therapy could lead to better treatment and reduced side effects, improving public health and lowering healthcare costs.
Wider Societal Implications: The project addresses critical healthcare challenges in cancer therapy and immune modulation, potentially offering new treatments. The active dissemination of findings and engagement in events like International Women and Girls in Science Day promotes scientific awareness and inspires individuals, especially women, to pursue STEM careers.