Technology
Technology
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
Key publications
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).
DOI: https://doi.org/10.1016/j.ymeth.2012.07.005
Phage display engineered T cell receptors as tools for the study of tumor peptide-MHC Interactions
Løset GÅ, Berntzen G, Frigstad T et al. Front Oncol. 2015 Jan 12;4:378 (review).
DOI: 10.3389/fonc.2014.00378
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.
DOI: https://doi.org/10.1038/srep39066
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.
DOI: https://doi.org/10.1053/j.gastro.2018.12.013
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)
DOI: https://doi.org/10.3390/antib8020032
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
DOI: https://doi.org/10.1073/pnas.1902836116
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
DOI: 10.1126/sciimmunol.
Affinity maturation of TCR-like antibodies using phage display guided by structural modeling
Frick R, Høydahl LS, Hodnebrug I et al. Protein Eng Des Sel. 2022 Feb 17;35: gzac005
DOI: https://doi.org/10.1093/protein/gzac005