NextCore is our unique drug development platform.
NextCore mimics the pivotal interaction between Antigen Presenting Cells (APC) and T helper cells (Th)
Harnessing the core of T cell immunity
T helper cells are the converging point in the adaptive immune cascade where they upon stimulation by HLA II molecules displaying peptide antigens orchestrate activation of other immune effector cells
Developing drugs that focus on these HLA II interactions will lead to a new level of specificity in therapeutic development – therapies that focus on the core of autoimmune and chronic diseases, as well as unique point of attack in cancer immunotherapy
NextCore allows for the first time to bring this drug and target space into a recognized industrial application building on next generation phage display technology
NextCore-HLA has a unique capacity to generate large combinatorial libraries of peptide HLA class II repertories enabling novel target discovery in a segment that previously was impossible
NextCore drug discovery platform facilitates development of cognate drugs targeted towards HLA cell surface markers. We have successfully developed TCRs and TCR-like antibodies with unique binding specificities for autoimmune antigens suitable for both ACT and antibody-based therapies such as ADC.
NextCore-HLA: Highly diversified antigenic peptide libraries (>1010) displayed on phages in the context of relevant HLA class II
Mix with disease relevant T-cells from patients
Recover the complexes that are bound. The receptor of the T-cells (TCR) is the target for the HLA II with the right antigenic peptide
Deciphering the antigenic peptide by using deep sequencing
Simplifying drug development for complex diseases
Next generation phage display by use of pVII and pIX as display scaffolds.
Løset GÅ, Sandlie I. Methods 2012 Sep;58 (1): 40-6 (review).
Multivalent pIX phage display selects for distinct and improved antibody properties.
Høydahl LS, Nilssen NR, Gunnarsen KS et al. Sci Rep. 2016 Dec 14;6:39066.
Plasma cells are the most abundant gluten peptide MHC-expressing cells in inflamed intestinal tissues from patients with celiac disease.
Høydahl LS, Richter L, Frick R et al. Gastroenterology 2019 Apr;156(5):1428-1439.e10.
Targeting the MHC Ligandome by Use of TCR-Like Antibodies.
Høydahl LS, Frick R, Sandlie I et al. Antibodies (Basel). 2019 Jun; 8(2): 32 (Review)
Affinity-engineered human antibodies detect celiac disease gluten pMHC complexes and inhibit T-cell activation.
Frick R, Høydahl LS, Hodnebrug I et al. bioRxiv 2019.
B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells.
Huszthy PC, Gopalakrishnan RP, Jacobsen JT et al. Proc Natl Acad Sci U S A. 2019 Dec 17;116(51): 25850
A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation
Frick F, Høydahl LS, Petersen J et al Sci Immunol. 2021 Aug 20;6 (62): eabg4925