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Custom Antibodies Against Autoimmune Diseases Using Human Phage Display

Looking to discover targeted immunotherapies for autoimmune diseases?

  • World’s first autoimmune libraries
  • Fully human antibodies
  • scFv and Fab formats available

Need a reliable method for discovering high-quality antibodies to diagnose or treat human autoimmune diseases?

Discover our world’s first human autoimmune antibody phage display library. These unique libraries are a rich source of high-affinity antibodies targeting specific autoimmune antigens, ready to be developed into the next ground-breaking autoimmune conditions

 

 

Interested in customizing your autoimmune antibody?

Optimize your antibody’s developability and take benefit from our advanced customization options tailored to your specific requirements. Get a comprehensive solution for all your custom autoimmune disease diagnostics and therapies with the help of our antibody experts!

Why choose ProteoGenix for your Custom Autoimmune Immunotherapy Discovery Needs ?

The World's First Autoimmune Antibody Library

Experience accelerated target therapy discovery and market entry with our unique human autoimmune library.

IP free

You have exclusive ownership of the custom-generated monoclonal antibodies targeting autoimmune diseases.

Binders guaranteed

Get at minimum three distinct antibodies specifically binding to your autoimmune-specific antigen(s).

Pre-built phage display libraries

Streamline your process and save valuable time and resources by leveraging our pre-built human autoimmune phage display libraries.

Fully human antibodies

Take advantage from our expertise and get your fully human clinical antibodies, without the need for humanization.

Integrated Services

Minimize your efforts with our additional services, including customized antigen production and comprehensive antibody developability assessment. We handle it all for you!

Flexible Antibody Development

Safeguard your antibody investment through milestone-based services designed for complex and high-risk projects.

Decreased Time to Market

Take advantage from our pre-built autoimmune libraries offering the advantages of customized libraries from immunization, combined with the efficiency of reduced delivery time found in naïve libraries.

Custom Human Autoimmune Antibody Discovery Workflow

  1. Your autoimmune-specific antigen can be acquired by:
  • Delivering the antigen to ProteoGenix
  • Allowing ProteoGenix to make the antigen for you (preferred)

2. Autoimmune Library Screening and Biopanning

  • Screening our pre-built autoimmune library for antigen binders
  • 4-6 rounds of biopanning

3. ELISA Screening of Single Phage Binders

  • Further validate binders by ELISA screening until at least 3-10 different binders have been identified

4. DNA Extraction & Antibody Sequencing

Recombinant antibody production

Therapeutic antibody production

Stable Cell Line Development

ADC development

Bispecific and Trispecific Antibodies

Antibody Developability

Antibody Phage Display Advantages for Producing Custom Anti-autoimmune Antibodies

Are you in search of a game-changing solution for developing custom anti-autoimmune antibodies ? Look no further than antibody phage display, a revolutionary technology that is transforming the field of antibody discovery. Antibody phage display can produce tailor-made antibodies targeting autoimmune disease-specific antigens. Here are some reasons why this antibody discovery method is most suited for identifying novel autoimmune antibodies :

  • Unparalleled Diversity

    Antibody phage display libraries offer a vast repertoire of diverse antibodies for precise targeting of autoimmune antigens.

  • Superior Targeting and Safety

    Antibody phage display enables the isolation of high-affinity, specific antibodies with minimized risk of off-target effects.

  • Accelerated Time-to-Market

    Streamlined processes and expertise ensure faster delivery of custom anti-autoimmune antibodies.

  • Expert Guidance

    Access our team of antibody experts for personalized support throughout the development process.

The benefits of antibody phage display for making custom monoclonal anti-autoimmune antibodies are not possible without the perfect phage display library.

The World’s First Pre-built Human Autoimmune Antibody Library

The probability that antibody phage display will deliver high-performing human autoimmune therapeutic or diagnostic antibodies is significantly increased when the library is engineered using the following factors :

  • The B-cells are derived from human tissue donors

  • The B-cells exist in an autoimmunity microenvironment

  • The library is of superior quality (excellent in-frame frequency and clone numbers)

ProteoGenix is proud to state that our antibody experts made such a library. In fact, we made the world’s first human autoimmune antibody phage display library designed to supercharge human autoimmune antibody discovery and market entry.

This pre-built antibody library represents an array of high-affinity autoimmune-specific antibodies. Unlike traditional custom libraries derived from immunized (non-human) hosts, our libraries offer a rich source of diverse antibodies. Here’s why our libraries are a game-changer:

  • Unmatched Diversity:

    With over 10^11 unique antibody clones and an exceptional in-frame frequency exceeding 94%, our libraries provide an expansive range of novel autoimmune immunotherapies waiting to be explored.

  • Rapid Delivery, Reduced Cost:

    Our pre-built human autoimmune antibody libraries offer the advantage of swift delivery and cost reduction. We eliminate the time-consuming process of custom library construction, enabling you to access high-performing antibodies quickly and efficiently.

Library Name Species Clone Number
LiAb-SFAUTOIMMTM Library Human Donors (42 patients with 7 different autoimmune diseases):
  • Sjogren’s Syndrome
  • Psoriasis
  • Psoriatic Arthritis
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus
  • Crohn’s Disease
  • Ulcerative Colitis
  • 1.08x1011(scFv)
  • 1.06x1011(Fab)

Customized Monoclonal Antibodies for Autoimmune Targets

With ProteoGenix’s cutting-edge human autoimmune libraries, you can rapidly discover high-performing monoclonal antibodies that bind specific autoantigens. Our antibody phage display service also provides exclusive access to IP-free DNA sequences for three high-affinity binders tailored to your target autoantigen.

Experience unmatched efficiency with our streamlined project timeline. From antigen design and purification to delivery of antibody DNA sequences, we can complete each project in just 8 weeks. This rapid turnaround sets us apart in the market, saving you valuable time and ensuring prompt progress.

ProteoGenix goes the extra mile to minimize your efforts by offering additional services that cater to your needs:

By entrusting your challenging autoimmune immunotherapy projects to our team of antibody experts, you can free up your valuable time, resources, and costs. With the added advantage of our antibody expression, developability assessment, and customization services, you’ll expedite your journey to the clinic while maximizing your efficiency and success.

Maximizing Antibody Clone Diversity while Minimizing Construction Bias

  • Conventional method :

    Kappa and lambda light chains are merged during processing, limiting clone diversity and introducing construction bias.

  • Our approach :

    Kappa and lambda light chains are processed separately, unlocking unparalleled clone diversity with minimal construction bias.

What this unlocks ?

 
  • Higher affinity :

    Greater odds of finding high-affinity binders

  • No cross-reactivity :

    Even against autoimmune neoantigens and conserved human antigens

  • Clinical-ready quality :

    Antibodies built to advance into clinical development

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How autoreactive antibodies arise ?
Exploring Future Immunotherapies

In the early stages of autoimmune disease, a breach in self-tolerance drives the immune system to attack the body’s own healthy tissue.Loss of self-tolerance
The immune system loses the ability to distinguish self-antigens from non-self antigens, breaching self-tolerance.

  1. Loss of self-tolerance

The immune system loses the ability to distinguish self-antigens from non-self antigens, breaching self-tolerance.

2. Autoreactive T and B cells expand

This breakdown drives the expansion of autoreactive T cells and B cells. B cells mount an antibody-dependent attack against healthy tissue.

3. Antibodies captured for clinical use

B cells collected from the blood of an autoimmune patient provide a diverse repertoire of autoreactive antibodies, ready for clinical use.

Affinity Maturation Produces Anti-Autoimmune Antibodies with High Affinity

  • Natural affinity maturation

    An immune phage display library sourced from autoimmune patients offers a diverse repertoire of antibodies that have already undergone natural affinity maturation and selection against autoimmune antigens — giving exceptional binding affinity and therapeutic potential that surpasses naive libraries built from healthy donors.

  • Lower immunogenicity risk

    Because the library is human-derived, the risk of immune reactions and adverse effects in therapeutic applications is significantly reduced compared to non-human sources — a key step toward safer, more effective autoimmune treatments.

Characteristics of Antibodies from Human Autoimmune Phage Display Library

Antibodies derived from our human autoimmune phage display libraries represent a uniquely valuable resource for your therapeutic development program, thanks to their inherent ability to target autoantigens with exceptional precision. Having likely undergone affinity maturation within the autoimmune microenvironment itself, these antibodies are naturally optimized to deliver more precise and potent therapeutic interventions than antibodies sourced from healthy or immunized donors.

Each library we generate is an untapped source of diverse, highly specific antibodies, giving you a genuine competitive advantage in the development of groundbreaking treatments for autoimmune conditions and opening pathways to therapeutic candidates that would be difficult to obtain through conventional approaches.

Naive Antibody Library (Human Donor) Immune Antibody Library (Human Donor) Immune Library (Non-Human Host)
Source Healthy Human Donors Autoimmune Patients Immunized Animals (non-human)
Antibody Diversity Broad Autoimmune Antigen Skewed Immunized Antigen Skewed
Target Specificity Limited Antigen-specific Antibodies Increased Autoimmune-specific Antibodies Increased Antigen-specific Antibodies
Affinity Maturation Minimal Affinity Maturation Affinity Maturation to Autoantigens Affinity Maturation to Immunized Antigen
Immunogenicity Risk Fully Human – Minimal Immunogenicity Risk Fully Human – Minimal Immunogenicity Risk Risk of an Immune System Reaction
Clinical Translation May Require Additional Optimization and Engineering Accelerated Leads for Autoimmune-Specific Therapies and Diagnostics May require further Characterization and Optimization

What is Autoimmunity?

Autoimmunity refers to the immune system attack of healthy cells, tissues, and other normal components of the body in the field of immunology. When this immune response results in a disease, it is known as an “autoimmune disease.”

Autoimmunity refers to the presence of antibodies or T cells that react with the body’s proteins. It is observed in all individuals, even in a healthy state. However, if this self-reactivity leads to tissue damage, it can result in autoimmune diseases.

Notable examples of such diseases include celiac disease, post-infectious irritable bowel syndrome (IBS), type 1 diabetes mellitus, Henoch–Schönlein purpura (HSP), sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto’s thyroiditis, Graves’ disease, idiopathic thrombocytopenic purpura, Addison’s disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). The most common treatment for autoimmune diseases are steroids.

Loss of Self Tolerance in Autoimmunity

Loss of self-tolerance can lead to autoimmunity because it disrupts the immune system’s ability to distinguish between “self” and “non-self” antigens. In a healthy immune system, there are mechanisms in place to recognize and tolerate the body’s cells and tissues, while mounting an immune response against foreign substances or pathogens.

  • Central Tolerance

    Self-tolerance is primarily maintained through a process called central tolerance, which occurs in the thymus and bone marrow. During this process, immune cells called T cells and B cells undergo education and selection to eliminate those that would react against the body’s proteins. However, in some cases, this process can be imperfect, leading to the survival of self-reactive lymphocytes.

  • Peripheral Tolerance

    Additionally, peripheral tolerance mechanisms function outside the primary lymphoid organs to prevent autoreactive lymphocytes from causing harm. These mechanisms include regulatory T cells that suppress immune responses against self-antigens.
    When self-tolerance is compromised, autoreactive lymphocytes can escape elimination or regulation and recognize and attack the body’s cells and tissues. This results in chronic inflammation and tissue damage, characteristic of autoimmune diseases. While the exact mechanisms causing loss of self-tolerance are not fully understood they likely involve genetic predispositions, environmental triggers, and dysregulation of immune checkpoints.

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How is a Phage Display Library Made?

  1. Extract & convert mRNA

mRNA is extracted from human or animals B-cells and reverse-transcribed into cDNA

2. Amplify variable regions

PCR generates the heavy and light chain variable regions using the antibody cDNA as a template

3. Insert into phage vector

The variable regions are inserted into a modified phage display vector. This vector is designed to express the antibody variable regions as a fusion protein alongside a coat protein on the phage’s surface. The antibodies are “displayed” on the phage’s exterior, while the DNA encoding the antibody remains enclosed inside the phage particle.

4. Screen, isolate & sequence

  • The library can be subjected to screening against a specific target antigen to detect phages that exhibit antibodies capable of binding to the target.
  • The phages that successfully bind to the target can be isolated, allowing for the elution of bound phages.
  • By sequencing the DNA encoding the antibody from these phages, the desired antibody can be produced for further examination or therapeutic applications.

The Difference Between Immune Libraries and Naïve Libraries

  • Naive Library

    A naive library is built by incorporating genes from an organism that has never encountered the antigen of interest. It offers a broad assortment of antibodies that have not undergone any antigen driven selection. This lack of prior selection increases the potential for discovering novel antibodies with distinctive binding properties, since the full diversity of the immune repertoire remains available.

  • Immune Library

    An immune library is built by incorporating genes from an organism that has been immunized with the antigen of interest. It consists of antibodies that have already undergone selection based on their capacity to bind that specific antigen. This makes immune libraries particularly valuable for swiftly identifying antibodies with high affinity.

The primary distinction between the two lies in the origin of the genes used in their construction. Naive libraries draw on a wide range of antibodies that have never encountered the antigen of interest, while immune libraries comprise antibodies specifically chosen for their proven ability to bind that particular antigen.

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Single Chain Variable Fragment (scFv) Antibody Format

A single-chain variable fragment (scFv) is a fusion protein composed of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins. It is connected by a brief peptide linker, typically consisting of approximately 10 to 25 amino acids. The linker peptide is often rich in glycine, which imparts flexibility and may contain serine or threonine to enhance solubility. The linker serves to connect either the N-terminus of the variable heavy chain (VH) to the C-terminus of the variable light chain (VL), or vice versa.

Single Chain Variable Fragment (scFv) Format Advantages

Single-chain variable fragments (scFv) offer a range of advantages compared to the parental monoclonal antibody (mAb) format, as highlighted below:

  • Smaller size :

    scFv molecules have a compact structure, enabling better tissue penetration and improved access to target sites.

  • Easy production and purification :

    The smaller size of scFv simplifies production and purification processes, resulting in higher yields and cost savings.

  • Recombinant DNA technology :

    scFv can be produced using recombinant DNA technology, allowing for efficient and scalable production in various expression systems.

  • Versatile engineering options :

    scFv molecules can be engineered to have multimeric forms and/or multivalency, enhancing their binding affinity and specificity compared to the parental mAb.

  • Neutralizing capacity :

    scFv antibody fragments can be effective in neutralizing the activity of specific autoantigens.

These advantages make scFv an attractive choice for therapeutic and diagnostic applications, offering improved properties and potential for optimization in antibody-based treatments

Fragment Antigen Binding (Fab) Antibody Format

The fragment antigen-binding (Fab) region is a segment of an antibody that links to antigens. It comprises one variable and one constant domain from both the heavy and light chains. The variable domain encompasses the paratope, which is part of the antibody that binds to the antigen and contains a group of complementarity-determining regions located at the N-terminus of the monomer. This arrangement enables each arm of the Y-shaped antibody to attach to an epitope on the antigen. 

Fragment Antigen Binding (Fab) Format Advantages

The fragment antigen-binding (Fab) antibody format provides several advantages compared to full-length monoclonal antibodies (mAbs), as outlined below:

  • Smaller size :

    Fab fragments are significantly smaller than full-length mAbs, enabling improved tissue penetration and accessibility to target sites.

  • Reduced immunogenicity :

    The smaller size of Fab fragments reduces the likelihood of triggering an immune response, making them less immunogenic.

  • Cost-effective production:

    Fab fragments can be produced more efficiently and cost-effectively compared to full-length mAbs, leading to potential cost savings.

  • High specificity:

    Fab fragments exhibit high specificity for their target antigens, allowing for precise and targeted binding.

  • Versatile applications:

    Fab fragments can be engineered for various applications, including drug delivery, imaging, and targeting specific antigens in tumors or other tissues.

  • Diagnostic and therapeutic potential:

    The high specificity and tissue penetration of Fab fragments make them valuable in diagnostic assays and as potential therapeutics for diseases such as autoimmune and infectious diseases.

  • Broad applicability:

    Neutralizing capacity: Fab antibody fragments can be effective in neutralizing the activity of specific autoantigens.

The unique features of the Fab antibody format position it as an attractive option for various applications, offering improved performance, versatility, and cost-effectiveness compared to full-length mAbs.

 

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