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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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References

Carey BS, Poulton KV, Poles A. Factors affecting HLA expression: A review. Int. J. Immunogenet. 2019 Oct;46(5):307-320

Fung MK and Benson K. Using HLA typing to support patients with cancer. Cancer Control 2015 Jan;22(1):79-86

Hirayama M and Nishimura Y.The present status and future prospects of peptide-based cancer vaccines.International Immunology, Volume 28, Issue 7, July 2016, Pages 319–328

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

Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, Litzky L, Bagg A, Carreno BM, Cimino PJ, Binder-Scholl GK, Smethurst DP, Gerry AB, Pumphrey NJ, Bennett AD, Brewer JE, Dukes J, Harper J, Tayton-Martin HK, Jakobsen BK, Hassan NJ, Kalos M, June CH. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013 Aug 8; 122(6): 863–871

Mompó SM, González-Fernández A. Antigen-Specific Human Monoclonal Antibodies from Transgenic Mice. Methods Mol Biol.2019;1904:253-291

Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA. Cancer regression and neurologic toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother. 2013 Feb; 36(2): 133–151

Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2. Mol Ther. 2010 Apr; 18(4): 843–851

Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Clinical Trial:Nature 2017  Jul 13;547(7662):217-221

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)

Schumacher TN and Schreiber RD. Neoantigens in cancer immunotherapy. Science 2015 Apr 3;348(6230):69-74

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

Timothy T Spear TT, Evavold BD, Baker BM, Nishimura MI. Understanding TCR affinity, antigen specificity, and cross-reactivity to improve TCR gene-modified T cells for cancer immunotherapy. Cancer Immunol Immunother. 2019 Nov;68(11):1881-1889

Wang M, Yao LC, Cheng M, Cai D, Martinek J, Pan CX, Shi W, Ma AH, De Vere White RW, Airhart S, Liu ET, Banchereau J, Brehm MA, Greiner DL, Shultz LD, Palucka K, Keck JG. Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy. FASEB J . 2018 Mar;32(3):1537-1549