B7-1/CD80 Chimeric Monoclonal Antibody (Clone IDEC-114 (Galiximab))

CD80, also known as B7-1, is a glycoprotein and member of the CD28/B7 family of co-stimulatory receptors that promotes T cell activation.^1,2 Alternative splicing of CD80 produces one full-length long isoform, CD80 long, and two short isoform, s1CD80 and s2CD80.² CD80 long exists as a membrane-bound dimer and is composed of an extracellular immunoglobulin variable (IgV) domain that interacts with the co-stimulatory molecule CD28 or the inhibitory molecule CTLA-4, as well as an immunoglobulin constant (IgC) domain and a cytoplasmic tail that are both required for T cell co-stimulation.¹ s1CD80 and s2CD80 lack the transmembrane domain or the transmembrane domain and the IgC domain, respectively, and are found in the serum.² CD80 is transiently expressed on the surface of antigen-presenting cells (APCs) and is upregulated following ligation of the co-stimulatory molecule CD86, as well as by pro-inflammatory stimuli, such as LPS, and downregulated by the anti-inflammatory cytokine IL-10.^3,4,5 CD80 has two ligands, CD28 and CTLA-4, that compete for binding and are each expressed on naïve T cells but have opposing functions on T cell activation.⁶ CD80 binding to CD28 promotes T cell activation, survival, and cytokine production, whereas CD80 binding to CTLA-4 inhibits T cell activation and promotes T cell anergy. Neutralization of CD80 with a monoclonal antibody reduces the severity of synovitis and bone erosion, as well as CD4⁺ T cell infiltration, in the inflamed joints of a mouse model of arthritis induced by complete Freund's adjuvant (CFA) and BSA.⁷ Decreased CD80 tumor levels have been identified in patients with renal cell carcinoma.⁸ CD80 SNPs have been found in individuals with gastric cancer.⁹ Cayman’s B7-1/CD80 Chimeric Monoclonal Antibody (Clone IDEC-114 (Galiximab)) was produced recombinantly from the original IDEC-114 antibody sequence and can be used for ELISA, flow cytometry (FC), immunohistochemistry (IHC), immunoprecipitation (IP), and Western blot (WB) applications and in functional assays.^10,11 The IDEC-114 antibody was prepared by immunizing cynomolgus monkeys with recombinant CD80 antigen. The variable regions of the light and heavy chains were then cloned by incorporation into an N5LG1 cassette vector containing human constant region genes and subsequently transfected into the Dg44 CHO cell line.

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2. Kakoulidou, M., Giscombe, R., Zhao, X., et al. Human soluble CD80 is generated by alternative splicing, and recombinant soluble CD80 binds to CD28 and CD152 influencing T-cell activation. Scand. J. Immunol. 66(5), 529-537 (2007).

3. Mir, M.A. Costimulation in lymphomas and cancers. Developing costimulatory molecules for immunotherapy of diseases 185-254 (2015).

4. Sahoo, N.C., Rao, K.V.S., and Natarajan, K. CD80 expression is induced on activated B cells following stimulation by CD86. Scand. J. Immunol. 55(6), 577-584 (2002).

5. Zhou, F., Ciric, B., Li, H., et al. IL-10 deficiency blocks the ability of LPS to regulate expression of tolerance-related molecules on dendritic cells. Eur. J. Immunol. 42(6), 1449-1458 (2012).

6. Buchbinder, E.I., and Desai, A. CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am. J. Clin. Oncol. 39(1), 98-106 (2016).

7. Odobasic, D., Leech, M.T., Xue, J.R., et al. Distinct in vivo roles of CD80 and CD86 in the effector T-cell responses inducing antigen-induced arthritis. Immunology 124(4), 503-513 (2008).

8. Flörcken, A., Johannsen, M., Nguyen-Hoai, T., et al. Immunomodulatory molecules in renal cell cancer: CD80 and CD86 are expressed on tumor cells. Int. J. Clin. Exp. Pathol. 10(2), 1443-1454 (2017).

9. Wu, R., Li, F., Zhu, J., et al. A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population. Med. Oncol. 31(8), 60 (2014).

10. Schopf, R.E. IDEC-114 (IDEC). Curr. Opin. Investig. Drugs 2(5), 635-638 (2001).

11. Vinjamaram, S., Czuczman, M.S., and Hernandez-Ilizalituri, F.J. The use of galiximab in non-Hodgkin lymphoma. Clin. Lymphoma Myeloma 8(5), 277-282 (2008).