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Applications that use HLA typed cells

In the development of cancer immunotherapies, it is frequently critical to have primary cells from various tissues with a specific HLA genotype. The main areas for application of HLA typed primary cells are

  • For development of engineered TCRs to optimally select for HLA-TCR- peptide complex with the highest immunogenicity
  • For development of therapeutic antibodies known as TCR like antibodies targeting the peptide MHC (pMHC antibodies) 
  • Cross reactivity testing across multiple tissue types for assessment of risk of development of cytokine storm or direct cytotoxicity
  • For studying the development of anti-drug antibodies (ADAs)
  • For development of neo-antigen peptide vaccines in cancer therapeutics 

Thus, HLA information is a critical piece of information needed in the development of preclinical invitro assays in the immune oncology drug discovery field.

Basics of HLA

MHC proteins supports self (our normal cells and tissues) vs non self-recognition (pathogens or modified self/cancer), in coordination with T Cell Receptor proteins(TCR) . T cells recognize foreign antigen/non- self peptide as a complex with MHC. Three classes of HLA exists in humans. MHC Class I is found on all nucleated cells in the body. Three major genes (A, B, C) comprise the Class I locus. MHC class I proteins displays peptides from within cells to T cells. Class II is found in addition to class I on antigen-presenting immune cells such as dendritic cells, B-cells, monocytes, macrophages. There are 6 main class II genes (DPA1, DPB1, DQA1, DQB1, DRA, DRB1). MHC class II displays peptides derived from exogenous antigens such as bacteria or viruses.. HLA-I molecules are both polygenic—being encoded by three genes (HLA-A, HLA-B, and HLA-C)—and highly polymorphic, with over 10,000 distinct alleles described thus far. The combination of multiple genes and alleles ensures enough diversification of HLA molecules to bind and present a wide range of peptides for T cell recognition and activation

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Products and solutions

Our portfolio of research and manufacturing media, non-viral transfection technologies and primary cells, supports you through every step of the cell and gene therapy process.

Therapy applications using hematopietic and stem cells

Immune responses to protein therapeutics are desired, such as when developing a vaccine

References

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Høydahl LS, Frick R, Sandlie I, Løset GÅ. Targeting the MHC Ligandome by Use of TCR-Like Antibodies. Antibodies 2019 May 9;8(2):32

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Schultz HS, Reedtz-Runge SL, Bäckström BT, Lamberth K, Pedersen CR, Kvarnhammar AM; ABIRISK consortium. Quantitative analysis of the CD4+ T cell response to therapeutic antibodies in healthy donors using a novel T cell: PBMC assay. PLoS One 2017 May 31;12(5)

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Sullivan A, Watkinson J, Waddington J, Park BK, Naisbitt DJ. Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions. Expert Opin Drug Metab Toxicol 2018 Mar;14(3):261-274

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