Monoclonal Antibody Development Targeting CD40-CD40L for Autoimmune Diseases

Blocking the cluster of differentiation (CD) 40-CD40 ligand (L) pathway is considered an effective way to treat autoimmune diseases. However, clinical trial testing shows that the blockade of the CD40-CD40L pathway in the treatment of systemic lupus erythematosus (SLE) is disappointing. Therefore, it is urgent to discover a novel therapeutic strategy to defeat SLE and other autoimmune diseases. Creative Biolabs offers monoclonal antibody (mAb) development services targeting CD40-CD40L to promote the treatment of autoimmune diseases. With expertise in antibody discovery, we can provide flexible solutions for your choice. Either stand-alone service or integrated project is both welcome to meet every specific demand in your antibody discovery project.

Short Introduction to Cluster Differentiation (CD) 40 (CD40)-CD40 Ligand (L)

CD40 is a costimulatory protein that was found on antigen-presenting cells. CD40 receptor is a member of the tumor necrosis factor receptor (TNFR) superfamily. This receptor is essential in mediating a broad variety of immune and inflammatory responses. CD40L was initially identified on the surface of the activated cluster of differentiation 4 (CD4). The interactions between B lymphocytes (B) cells, T lymphocytes (T) cells, and CD40-CD40L were important for germinal center (GC) responses.

Fig.1 The critical role of the CD40 ligand (CD40L)-CD40 dyad in the inflammatory response underlying multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE).^{1, 3}

CD40-CD40L and Autoimmune Diseases

The CD40 pathway plays an important role in autoimmune disease. A study showed that compared to healthy groups, in systemic lupus erythematosus (SLE) groups, CD40L expression was elevated on various cell subsets (B cells, T cells, and monocytes). CD40L expression was also increased in circulating T cells from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

A survey in the kidney showed that CD40 was not normally expressed in healthy kidneys but was upregulated by podocytes of glomeruli in individuals with focal segmental glomerulosclerosis (FSGS). It should be noted that FSGS can result in autoimmune nephritis. This example also illustrates the link between CD40 and autoimmune diseases.

A study in several autoimmune skin diseases found that in the skin, CD40 was expressed in healthy keratinocytes, but can be greatly upregulated in autoimmune skin diseases, such as systemic sclerosis (SSc) and SLE. In SLE, but not healthy donors, CD40L+ infiltrating lymphocytes are present in skin lesional biopsies.

Fig.2 CD40L ability to drive inflammation in non-lymphoid tissues.^{2, 3}

Treatment of Autoimmune Diseases by CD40-CD40L

It is consistent with the treatment of autoimmune diseases by CD80/86-CD28, blockade of the CD40-CD40L pathway is also a therapy for autoimmune diseases. One of the first molecules that were generated to target the CD40 pathway was a CD40L-specific humanized IgG1 mAb. Scientists indicated that blockade of the CD40 pathway can modulate key clinical parameters of lupus and highlighted the immunomodulatory potential of CD40-CD40L blockade in autoimmunity.

Custom Services of Monoclonal Antibody Development Targeting CD40-CD40L

Based on CD40-CD40L, Creative Biolabs provides a comprehensive range of customized, high-quality services in mAb development to support the drug industry and related biomedical sciences research communities worldwide. We have developed various antibody discovery platforms to meet different demands.

Our team makes Creative Biolabs unique. We have 90% retention of our employees, a management team with an average of 10+ years of industry experience. Our staff has the operational grit and scientific background that you need for your success. We offer mAb development services targeting CD40-CD40L with the features of high affinity, high specificity, and high sensitivity. If you are interested in our services, please contact us.

References

1. Aarts, Suzanne ABM, et al. "The CD40–CD40L dyad in experimental autoimmune encephalomyelitis and multiple sclerosis." Frontiers in immunology 8 (2017): 1791.
2. Karnell, Jodi L., et al. "Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond." Advanced drug delivery reviews 141 (2019): 92-103.
3. Distributed under Open Access license CC BY 4.0, without modification.

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