Antibody Murinization (Convert to Mouse Ab) Service

Services Published Data FAQ Resources

Monoclonal Antibody Murinization

Creative Biolabs is proud to be the first company that offers professional monoclonal antibody murinization service. Relying on our unparalleled expertise in antibody engineering and affinity maturation, monoclonal antibodies with a variety of species background, such as human, rabbit, rat, chicken, bovine and dog can be successfully murinized without specificity switch and significant decrease in affinity.

Frequently, human therapeutic antibodies require a mouse counterpart so its efficacy can be tested in rodent animal models. In these cases, murinization of the human antibodies is the most straightforward method to achieve this goal. Based on our extensive experience in antibody humanization, we usually select the best matching murine antibody frameworks and then perform CDR grafting, which is then followed by construction and screening of a unique phage display library with designed mutation positions. In the end, multiple "murinized" mutants with the high affinity retained can be obtained.

Monoclonal Antibody Murinization Service

After murinization, the "murinized" frameworks greatly decrease their immunogenic in mice as compared to the parental antibody or chimeric murine-human antibody, and thus made them ideal antibodies for pharmacophore studies in rodents. In addition to our unique antibody murinization service, Creative Biolabs is one of the leading companies that is specialized in custom antibody humanization service.

Other optional antibody engineering services:

Published Data

Murinized Anti-IL-1b Antibody

Fig. 2 Anti‐IL‐1β treatment reduces serum FetA and urinary TNF‐α levels in diabetic DBA/2J mice. (Jana M. Orellana, 2017)

The study investigated the effects of Fetuin-A (FetA) and palmitic acid on podocyte death, highlighting the role of interleukin-1 (IL-1) signaling in exacerbating lipotoxicity in podocytes—a key factor in diabetic nephropathy (DN). In vitro experiments demonstrated that both FetA and lipopolysaccharide (LPS) intensified palmitic acid-induced podocyte death, which was strongly linked to an inflammatory response involving the secretion of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC). The murinized anti-IL-1b antibody played a critical role in attenuating the inflammatory and cellular death responses elicited by FetA and palmitic acid. In vivo experiments with diabetic DBA/2J mice treated with the anti-IL1-b antibody for four weeks demonstrated a preventative effect on the increase in serum FetA levels and a significant reduction in urinary tumor necrosis alpha (TNF-a) levels. The study underscores the significance of IL-1b signaling in the pathogenesis of DN, suggesting that inhibiting this pathway could be a promising strategy for the treatment and prevention of DN. The use of murinized antibodies against IL-1b specifically targets this pathway, providing a rationale for more prolonged in vivo studies to explore the therapeutic potential of anti-IL-1b therapy in DN.

Reference

Orellana, Jana M., et al. "Fetuin‐A aggravates lipotoxicity in podocytes via interleukin‐1 signaling." Physiological reports 5.10 (2017): e13287.

FAQ

What is antibody murinization?
Murinization is the process of modifying an antibody derived from a non-mouse species (commonly human) to resemble a mouse antibody while retaining its original antigen-binding specificity. This is achieved by grafting the variable regions of the human antibody onto the constant regions of a mouse antibody. This technique is often used to reduce the immunogenicity of therapeutic antibodies in mouse models during preclinical testing.
Why is murinized antibody important in research?
Murinized antibodies are crucial in biomedical research, particularly in the development and testing of therapeutic antibodies. By using antibodies that are structurally similar to mouse antibodies, researchers can effectively study the efficacy, pharmacokinetics, and immunological properties of these antibodies in mouse models, which are commonly used to mimic human disease states prior to clinical trials.
How is antibody murinization performed?
The process of murinization involves several molecular biology techniques. First, the variable domains of the human antibody (VH and VL) that are responsible for antigen binding are identified and sequenced. These human variable domains are then genetically fused to the constant domains (CH and CL) of a mouse antibody. The resulting chimeric genes are then cloned into an expression vector, which is introduced into a suitable host cell line for antibody production.
How does murinization affect the efficacy of an antibody in preclinical models?
Murinization can affect antibody efficacy in several ways. By replacing the human constant regions with mouse constant regions, the interaction of the antibody with mouse effector cells and complement systems is optimized, potentially improving the efficacy of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in mouse models. However, changes in the antibody structure could also impact its binding affinity to the target antigen, which needs to be carefully evaluated during development.
Can murinized antibodies be used in human clinical trials?
Murinized antibodies are generally not used in human clinical trials due to their potential immunogenicity in humans. They are primarily used in preclinical studies to evaluate the biological efficacy of therapeutic antibodies in mouse models. For clinical trials involving humans, fully human or humanized antibodies are preferred as they are less likely to be recognized as foreign by the human immune system.
What are the main applications of murinized antibodies?
The primary application of murinized antibodies is in the preclinical phase of drug development, particularly for the evaluation of therapeutic antibodies in mouse models. These antibodies are used to study the pharmacodynamics, pharmacokinetics, and toxicology of potential therapeutic agents in a biologically relevant system that closely mimics human responses.
Are there alternatives to murinization in antibody development?
Alternatives to murinization include humanization and the development of fully human antibodies using phage display or transgenic mice that are capable of producing human antibodies. Humanization involves modifying a small portion of the non-human antibody to increase its similarity to human antibodies, reducing immunogenicity while retaining high specificity and affinity. Fully human antibodies are derived entirely from human gene sequences, thus minimizing the risk of immunogenicity in humans.