Elsenoor Klaver, Group Leader at Charles River discussed two main topics. Firstly, antigen-specific T cells for targeted immunogenicity and efficacy testing. Secondly, tonsil organoids for therapeutic manipulation of global adaptive immune responses.
Antigen-specific T cells are critical in recognising threats such as pathogens and cancers, and their role in autoimmunity. Klaver highlighted the challenges in preclinical research such as low precursor frequency of antigen-specific T cells and low expression of HLA molecules.
Charles River relies on a HLA stabilisation assay that tests for antigen-specific mechanisms by loading T2 cells with peptides to test binding strength and stability over time. This assay helps in selecting suitable peptides for generating an immunogenic response. The assay predicts the immunogenicity of unique vaccine candidates and shows their ability to drive expansion of rare antigen-specific T cells.
Furthermore, polyclonal expansion assays are set up using multimers to generate higher numbers of antigen-specific cells. Klaver mentioned stimulating peptides with MART-1 led to a nice expansion of CD8+ cells over a two-week period. Once a good number of antigen specific T cells have been generated, functional and killing assays are conducted to ensure the cells. functional and capable of killing target cells.
The presentation then shifted to how tonsil organoids are used to bridge the gap between preclinical studies and clinical effectiveness in vaccine development. The organoid structure comprises a complex 3D architecture and support germinal centre formation fpr therapeutic testing. Tonsil organoids are generated by dissociating tonsil tissue into single cell suspensions and setting up high-density transfer cultures.
Klaver presented a case study on the flu vaccines where they generated tonsil cultures and did a simulation for 7 - 10 days. They observed the formation of germinal centres, areas where B cells undergo maturation, class switching, and selection — essential processes for effective immune memory. Then she discussed the effect of immunomodulators like rapamycin and tofacitinib on tonsil organoids, showing how these substances impact B cell differentiation and the presence of specific immune cell subsets The organoids produced antigen-specific antibodies, including IgG and IgA, and generated memory B cells and plasma cells, key components of a durable immune response.
The results demonstrate that tonsil organoids can mimic human mucosal immune responses in a controlled lab setting. This model offers significant potential for vaccine testing, studying human-specific immune mechanisms, and reducing reliance on animal models.
