Creative Biolabs has extensive experience to offer the novel human or humanized antibody services for either therapeutic or laboratory applications. We have three routes in developing human antibodies. The first and most straightforward method is to screen our human antibody libraries. The second method is to immunize premade "humanized" mice and then raise hybridoma cell lines [or to create an immune humanized antibody library] that produce human antibodies. The third method is antibody humanization. We rely on animals to produce non-human antibodies using either hybridoma or immune antibody library screening and screening methods; after that, the top candidate is humanized.

Through the flourish of antibody based therapeutic drugs, the demand of human or humanized antibody is synchronized growth. Due to the potential risk of immunogenicity, the full human antibody or at least humanized antibody (from xenogeneic sources) is required for further clinical application. Because of the serious ethical and moral issues, it is obviously an impossible task to directly immunize human beings with interested antigens. Nevertheless, several techniques have been developed as alternative solutions to overcome this limitation. Creative Biolabs is able to provide human or humanized antibodies in the ethical standards category, three main aspects have been enumerated as followed:

Truly Human Antibody from Premade Human Antibody Libraries

Creative Biolabs owns several naive or synthetic human antibody libraries in-house with diversity of over 10⁹. These premade libraries are generally based on human antibody genes from non-immunized donors or human antibody repertoire and constructed in scFv or Fab format. In this way, these premade libraries are qualified for screening human antibodies specific binding to the target protein (or other molecules). Owe to the 100% human sources, the isolated antibodies carry rare risk to cause significant immunogenicity issue in therapeutic applications.

Fully Human Antibody from FHAT Transgenic Mice

Another choice for producing fully human antibody is utilizing the Fully Human Antibody Technology™ (FHAT) of Creative Biolabs. This technology is based on the creation of a mouse strain engineered to produce a large repertoire of human antibodies in the absence of mouse antibodies. Through introducing human immunoglobulin loci into the germline of mice deficient in mouse antibody production, the "humanized" transgenic mice (FHAT transgenic mice) are able to produce significant levels of antigen-specific human antibodies with high affinity and specificity.

Non-human Primate (NHP) Antibody Humanization

Creative Biolabs has developed the innovative Hi-Affi^TM platform to provide top-class humanization of non-human primate (NHP) antibody as a unique solution to develop therapeutic antibodies for human use. Compared with the commonly used rodent, NHP has much closer genetic relationship to that of human, which means that the antibodies isolated from immunized NHPs may have higher affinity and lower immunogenicity to human beings. On the other hand, the humanization of NHP antibody is much easier than other species, and potentially has no affinity loss under suitable technique.

Besides non-human primate, Creative Biolabs also provide humanization service to antibodies derived from other species, such as mouse, rat, rabbit, chicken, llama, dog, shark and more.

Learn more about Human or Humanized Antibody Services:

• Antibody Humanization
• Humanization of Monkey (NHP) Antibodies
• Humanization of Bovine Ultralong CDR3 Antibodies
• Humanized Antibody Germinalization Service

Published Data

• Human Monoclonal Antibody HMAb 9C7 to Neutralize All Four Serotypes of Dengue Virus

Fig. 2 Neutralization potency of HMAb 9C7 in BHK-21 cells. (Jiansheng Lu, 2022)

Dengue virus (DENV) causes about 100 million acute dengue cases and 21,000 deaths worldwide every year. Here, the researchers showed that the human monoclonal antibody (HMAb) 9C7 can bind to all four complete serotypes of DENV, but not to the recombinant envelope protein, indicating that HMAb 9C7 recognizes the conformational epitope of the envelope protein. The results showed that HMAb 9C7 neutralized all four serotypes of DENV in vitro. And anti-DENV-1 HMAb 9C7 showed activity in the pre-attachment and post-attachment steps of the virus life cycle. At the same time, HMAb 9C7 effectively protected suckling mice from all four serotypes of DENV. Therefore, HMAb 9C7 may be a drug that can prevent and treat DENV.

• A Fully Human Neutralizing mAb Targeting Human Cytomegalovirus Glycoprotein B

Fig. 3 Neutralizing activity of EV2038 in vitro. (Miwa Okamoto, 2023)

Human cytomegalovirus can cause serious diseases in children and immunocompromised patients. Here, the researchers studied the inhibitory effects of whole-human neutralizing monoclonal antibodies on human cytomegalovirus infection and virus-to-cell transmission. The scientists isolated a potent neutralizing antibody EV2038 (IgG1 lambda) that inhibits human cytomegalovirus infection in all four laboratory strains and 42 clinical isolates. In addition, EV2038 can prevent the intercellular transmission of eight clinical virus isolates. EV2038 can recognize three discontinuous sequences on glycoprotein B antigen domain 1, which are highly conserved in many clinical isolates. The data in this article show that EV2038 is expected to be a candidate and a new alternative drug for the treatment of human cytomegalovirus infection.

FAQ

1. What is the difference between human and humanized antibodies?

   Human antibodies are produced naturally by the immune system in humans. They are derived from B cells and are fully human in their protein structure, which minimizes the risk of immune reactions when used in therapeutic applications. Humanized antibodies, on the other hand, are originally derived from non-human species, typically mice. These antibodies are then genetically engineered by replacing most of the mouse protein sequences with human sequences while retaining the small regions critical for antigen binding. This process reduces the immunogenicity of the antibodies when used in human therapy, making them more suitable for repeated administration in chronic conditions.

2. Why are humanized antibodies important in medicine?

   Humanized antibodies play a crucial role in the treatment of chronic diseases such as cancer, autoimmune diseases, and various infectious diseases. Their importance lies in their ability to specifically target diseased cells or pathological molecules with minimal side effects compared to traditional drugs. By modifying mouse antibodies to resemble human antibodies more closely, humanized antibodies can be administered to patients without significant risk of immune rejection. This makes them effective tools in targeted therapies, where precision and reduced side effects are paramount.

3. What are the advantages of humanized antibodies?
   • Enhanced Specificity: Animal-derived antibodies often have high specificity and affinity for antigens. By humanizing these antibodies, researchers can retain the high specificity while reducing immunogenicity.
   • Broader Availability of Antigen Models: Animal systems can often elicit stronger immune responses to a broader range of antigens, which can then be humanized for therapeutic use.
   • Development Efficiency: The process of humanizing an antibody can sometimes be faster, particularly when starting from a well-characterized animal antibody that is known to be effective against the target.
4. What challenges are associated with the development of humanized antibodies?
   • Maintaining Affinity and Specificity: While transferring the complementarity-determining regions (CDRs) from a mouse to a human framework, there is a risk that the antibody may lose some of its binding affinity or specificity to the antigen. This necessitates additional engineering and fine-tuning to regain optimal function.
   • Immunogenicity Risks: Even with humanization, there is still a risk that the remaining non-human parts of the antibody may be recognized as foreign by the human immune system, potentially leading to immune responses that can reduce the efficacy of the treatment or cause adverse reactions.
   • Regulatory and Technical Complexities: The process of designing, developing, and validating humanized antibodies is complex and must meet stringent regulatory standards to ensure safety and efficacy. This requires extensive preclinical and clinical testing, which can be costly and time-consuming.
5. How do human and humanized antibodies contribute to the field of immunotherapy?

   Human and humanized antibodies are pivotal in the field of immunotherapy, particularly in the treatment of diseases where the immune system plays a key role, such as cancer, autoimmune disorders, and infections. These antibodies can be designed to perform a variety of functions, such as blocking the activity of a specific protein, marking cancer cells for destruction by the immune system, or modulating immune responses. For example, in cancer treatment, antibodies can be engineered to target and bind to cancer cell-specific antigens, leading to direct cell killing or recruitment of other immune cells to eliminate the tumor. In autoimmune diseases, these antibodies can help dampen overactive immune responses, thereby reducing inflammation and tissue damage.

6. What future developments are expected in the field of human and humanized antibodies?
   • Enhanced Targeting Capabilities: Ongoing research is focusing on improving the specificity and affinity of antibodies to target disease-related antigens more effectively. This includes the development of bispecific antibodies, which can bind to two different antigens simultaneously, offering new ways to engage and activate the immune system against cancers or other diseases.
   • Integration with Other Therapeutic Modalities: Combining humanized antibodies with other therapies such as chemotherapy, radiation, or emerging treatments like gene therapy and CAR-T cell therapy is a growing area of interest. These combinations aim to enhance overall treatment efficacy and overcome resistance mechanisms.
   • Application in New Therapeutic Areas: Beyond oncology and autoimmune diseases, humanized antibodies are being explored for use in other conditions such as allergic diseases, infectious diseases, and neurodegenerative disorders, expanding the potential impact of this technology.

Resources

Use the resources in our library to help you understand your options and make critical decisions for your study.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.