Gene Synthesis supports the development of
Therapeutic Antibodies
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:
GenScript's custom
Peptide Services offer:
GenScript's custom
Antibody Services offer:
GenScript's
Antibody Drug Development Center offer
Read more about how gene synthesis is playing a role in research and development of:
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.
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:
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.
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Gene synthesis enables customized recombinant and codon-optimized sequences encoding chimeric antibody-based drugs.
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ADCC & CDC assays enable studying the immune-stimulatory effect of antibody based drugs in-vitro.
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Orthotopic animal models enable studying the effect of tumor microenvironments on drug efficacy in-vivo.
The products and services in this section are for Research Use Only. Not for use in human clinical diagnostics or therapeutics or in vitro diagnostic procedures.
