Antibody Drug Discovery Solutions Made Simple

Therapeutic antibodies, specifically Monoclonal Antibodies, can activate, repress, or alter endogenous immune responses to specific cells or molecules. Antibody-based drugs are revolutionizing the treatment of cancer, inflammatory and autoimmune disease, and many other types of disease.

Genscript is the only company providing end-to-end antibody drug development. Gene Synthesis provides key advantages throughout the process of Antibody Drug Development:

Generate Therapeutic Antibodies with Support from the Leading Global Biotech Company

From custom bioreagents to antibody drug developments, GenScript offers a comprehensive range of services to aid in basic and translational biomedical research as well pharmaceutical research & development.

GenScript's Gene Synthesis can help you

• boost expression of antigenic peptides and proteins with Codon-optimized Gene Constructs.
• get custom DNA sequences encoding chimeric antibodies that you design Delivered In As Few As 4 Days.
• save time and money on Mutagenesis, Custom Cloning, Plasmid Preps, and other Molecular Biology Services.

GenScript's custom Peptide Services offer

• Antigen synthesis for antibody generation via Custom Peptide Synthesis
• Epitope mapping or hit identification via Custom Peptide Library Services

GenScript's custom Antibody Services offer

• Monoclonal and Polyclonal fast packages
• Premium Hybridoma Development
• Animal facility is AAALAC accredited and OLAW assured

GenScript's Antibody Drug Development Center offer

• Monoclonal Antibody Sequencing
• Epitope Mapping
• Affinity Maturation
• Chimeric Antibody Generation

Read more about how gene synthesis is playing a role in research and development of

• Neutralizing Antibodies for Inflammatory and Autoimmune Disease

  In contrast to antibodies used in cancer therapeutics, which aim to stimulate an immune attack, therapeutic antibodies for inflammatory and autoimmune diseases are designed to do the opposite: neutralizing antibodies bind to pro-inflammatory factors and prevent them from exacerbating the immune response. Two recently published studies developed antibodies to minimize FcR-mediated immune responses with the benefit of Gene Synthesis of full-length or truncated DNA sequences encoding immunoglobulin chains, Fc receptors, and other components of inflammatory signaling:

  • J Immunol. 2013 Sep. Chimeric Anti-CD14 IGG2/4 Hybrid Antibodies For Therapeutic Intervention In Pig And Human Models of Inflammation. Lau et al. designed chimeric anti-CD14 antibodies containing the IgG2/IgG4 hybrid Fc region, which minimizes FcγR binding and complement activation and makes these Abs suitable for therapeutic intervention in pig and human models of inflammation. In order to construct and characterize these Abs, they used Gene Synthesis of truncated gene sequences encoding FcRn as part of their rigorous testing of this new antibody's effects on Fc-mediated immune responses.
  • MAbs. 2013 May. Autoantibody Depletion Ameliorates Disease In Murine Experimental Autoimmune Encephalomyelitis. Challa et al. used FcRn-binding antibodies to enhance degradation of autoantibodies and ameliorate disease in the murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Autoantibodies are a hallmark of MS and other autoimmune diseases such as lupus and rheumatoid arthritis, and signaling through FcR regulates T-cell activation by self-peptides and generation of autoantibodies. To produce their desired recombinant IgG expression constructs, they ordered Gene Synthesis of specific heavy- and light-chain variable domains.
  • BMC Immunol. 2012 Apr. Prevalence of Collagen VII-specific Autoantibodies In Patients With Autoimmune And Inflammatory Diseases. Licarete et al. ordered gene synthesis of a sequence encoding a chimeric protein that enables a new, sensitive, specific ELISA immunoassay to detect collagen-specific antibodies. This tool will improve the routine diagnosis and disease monitoring in patients as well as supporting future clinical and translational research.
• Monoclonal Antibody Therapy for Cancer (Immuno-oncology)

  Therapeutic Monoclonal Antibodies (mAbs) are the market leader in the targeted cancer therapy space; include blockbusters trastuzumab (Herceptin^®) and rituximab (Rituxan^®). Monoclonal antibody therapy regimens may target tumor-specific antigens/receptors, or may block important pathways central to tumor growth and survival.

  Read about monoclonal antibodies developed using gene synthesis and antibody services from GenScript:

  Methods Mol Biol. 2013 Sep. Humanization And Simultaneous Optimization of Monoclonal Antibody Methods

  PLoS One. 2013 Jan. Isolation of A High Affinity Neutralizing Monoclonal Antibody Against 2009 Pandemic H1N1 Virus

• Antibody-Drug Conjugates

  Antibody-drug conjugates use mAbs to target cytotoxic drugs specifically to cancer cells. For example, brentuximab vedotin (Adcetris) for Hodgkin lymphoma combines an anti-CD30 monoclonal antibody + the cytotoxic agent monomethyl auristatin E (MMAE) which is released only upon internalization into CD30+ cancer cells.

  

  Read about antibody-drug conjugates developed using services from GenScript:

  • Proc Natl Acad Sci U S A. 2013 Oct. Identification And Grafting of A unique Peptide-binding Site In The Fab Framework of Monoclonal Antibodies.
  • Mol Ther. 2012 Aug. A New Biodegradable Anti-CD163 Antibody-drug Conjugate That Specifically Targets Dexamethasone To CD163 In Macrophages.
• Overcoming Challenges of Therapeutic Antibody Development

  Antibody drug development is not always straight-forward, but GenScript's gene synthesis and antibody engineering services can help overcome the challenges.

  Challenge #1: Selecting an antigen / target

  A protein expressed only by cancer cells and not by healthy cells can help avoid dangerous widespread autoimmunity. Targeting an immune checkpoint protein or a receptor that is manipulated by cancer cell signaling can help to overcome cancer-induced immunosuppression, e.g. CTLA-4 or PD-1.

  Types of Antigens used for antibody drug development include:

  • resected tumor cells
  • purified peptides
  • DNA that encodes peptide/protein antigens; these may prolong the antigen-stimulated immune response, as has been demonstrated in numerous DNA Vaccines
  • viral or cellular vectors that act as adjuvants to enhance antigenicity of the payload.

  Gene synthesis enables:

  • custom design of antigen sequences
  • mutant library construction for screening/discovery of novel potent antigens
  • codon-optimization for high-level expression of antigens
  • Custom vector construction allows customization of transgene, adjuvants, vector, and other elements to optimize safety and efficacy of DNA-based vaccines

  Challenge #2: Optimizing antibody specificity and production

  Monoclonal antibody production methods, such as Hybridoma Development, give us the ability to derive individual antibodies of invariant specificity and selectivity and to immortalize the antibody-producing cells, ensuring a virtually infinite supply of highly specific antibodies. However, hybridoma technology requires substantial time, labor, expertise, specialized cell culture facilities, lab animals, and the screening of large numbers of hybridomas. The number of substances that are immunogenic in mammals is limited, and the maximum diversity expected from the mammalian immune response is on the order of 6 x 106 different antibodies. More importantly, there is no practical way to alter the properties of antibodies produced by hybridomas.

  These challenges may be overcome through the use of hybrid chimeric antibodies in which the mouse variable and human constant regions are fused on a genetic level. Recombinant human-mouse antibodies of this nature retain the specificity of the original murine variable region but assume the effector function of the human constant region.

  Gene Synthesis enables

  • codon optimization to maximize expression of antibodies for downstream purification / characterization.
  • synthesis of DNA sequences encoding recombinant antibodies such as humanized mouse antibodies

  Antibody Sequencing enables further engineering of the antibody for optimization, and insures against loss of hybridomas.

  Antibody Affinity Maturation with phage display library enables fast screening to obtain antibodies with high specificity against the target antigen.

  Antibody Humanization enables chimerization of a monoclonal antibody, translating it into an antibody therapeutic that can be used in humans.

  Challenge #3: Overcoming immunosuppression e.g. in tumor microenvironments

  Chimeric molecules that combine immune-stimulatory cytokines with cancer-targeted antibodies can induce an effective localized immune response.

  • Gene Synthesis enables customized recombinant and codon-optimized sequences encoding chimeric antibody-based drugs.
  • ADCC & CDC Assays enable studying the immune-stimulatory effect of antibody based drugs in-vitro.
  • Orthotopic animal models enable studying the effect of tumor microenvironments on drug efficacy in-vivo.
• Read Peer-Reviewed Publications on Therapeutic Antibody Development

  GenScript has been on the forefront of supporting the development of therapeutic antibodies. Read the featured studies below, or search more than 8,400 Peer Reviewed Publications that cite GenScript.

  • J Immunol. 2013 Sep. Chimeric Anti-CD14 IGG2/4 Hybrid Antibodies for Therapeutic Intervention In Pig And Human Models of Inflammation.
  • J Biol Chem. 2013 Oct Two Novel Tau Antibodies Targeting The 396/404 Region Are Primarily Taken Up By Neurons And Reduce Tau Pathology.
  • PLoS Negl Trop Dis. 2013 Sep. A Neutralizing Monoclonal Antibody Targeting The Acid-Sensitive Region in Chikungunya Virus E2 Protects From Disease.
  • Mol Biol. 2013 Sep. Humanization And Simultaneous Optimization of Monoclonal Antibody Methods.
  • Nature. 2013 Aug Cross-neutralization of Four Paramyxoviruses By A Human Monoclonal Antibody.
  • MAbs. 2013 May. Autoantibody Depletion Ameliorates Disease In Murine Experimental Autoimmune Encephalomyelitis.
  • PLoS One. 2013 Jan. Isolation of A High Affinity Neutralizing Monoclonal Antibody Against 2009 Pandemic H1N1 Virus.
  • BMC Immunol. 2012 Apr. Prevalence of Collagen VII-specific Autoantibodies In Patients With Autoimmune And Inflammatory Diseases.
  • J Virol Methods. 2012 Mar. Characterization Of A Monoclonal Antibody Against The 3D Polymerase Of Enterovirus 71 And Its Use For The Detection Of Human Enterovirus A Infection.