CD40 Recombinant Monoclonal Antibody

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Description

Mechanism of Action

CD40 is broadly expressed on APCs (dendritic cells, B cells, monocytes), stromal cells, endothelial cells, and certain tumors . Agonistic CD40 recombinant mAbs mimic the natural CD40 ligand (CD40L) to:

  • Activate APCs: Upregulate MHC class II and costimulatory molecules (e.g., CD86), promoting T-cell priming .

  • Induce cytotoxic myeloid cells: Enable macrophage-mediated tumor stroma destruction .

  • Direct antitumor effects: Trigger apoptosis in CD40+ malignancies (e.g., B-cell lymphomas) .

  • Synergize with chemotherapy: Enhance antigen cross-presentation and T-cell infiltration via tumor cell death .

Antagonistic CD40 mAbs (e.g., lucatumumab) block CD40-CD40L interactions, suppressing autoimmune or inflammatory responses .

Table 1: Clinically Evaluated CD40 mAbs

Antibody NameClone/FormatActivityClinical FindingsSource
CP-870,89321.4.1 (IgG2)Strong agonist- 80–100% cure in murine lymphoma models .
- Partial responses in melanoma patients .
DacetuzumabSGN-40 (humanized IgG1)Partial agonist- Complete responses in non-Hodgkin’s lymphoma .
- Synergy with chemotherapy in myeloma .
Chi Lob 7/4IgG1Agonist- Phase I trials show transient cytokine release syndrome (CRS) .
LucatumumabIgG1Antagonist- Evaluated in hematologic malignancies .
MOB-120CQChimeric (mouse/human)Agonist- Activates B cells and T cells in vitro .
- Validated in WB, ELISA .

Antitumor Efficacy

  • In murine models, agonistic CD40 mAbs eradicated bulk tumors and established long-term immunity .

  • CP-870,893 induced rapid B-cell activation and margination, correlating with melanoma-specific T-cell responses .

  • Combination therapy: Gemcitabine + CD40 mAbs cured 50% of pancreatic cancer patients, with stromal destruction enhancing chemotherapy delivery .

Engineering Innovations

Next-generation CD40 mAbs focus on improving tumor selectivity and reducing systemic toxicity:

  • Fc engineering: Modified Fc regions (e.g., IgG2 for CP-870,893) optimize CD40 clustering and agonism without excessive CRS .

  • Bispecific formats: Targeting CD40 + tumor antigens (e.g., CD40-HER2) enhances tumor-localized immune activation .

  • In situ vaccination: Chemotherapy + CD40 mAbs convert "cold" tumors to "hot," enabling checkpoint inhibitor efficacy .

Challenges and Future Directions

  • Biomarker identification: Predictive markers for patient stratification remain elusive .

  • Dosing optimization: Balancing immune activation and CRS requires refined regimens .

  • Combination strategies: Ongoing trials explore CD40 mAbs with PD-1 inhibitors, chemotherapy, and vaccines .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Typically, we can ship the products within 1-3 business days of receiving your order. Delivery times may vary based on the purchasing method and location. Please consult your local distributors for specific delivery timelines.
Synonyms
AI326936 antibody; B cell associated molecule CD40 antibody; B cell surface antigen CD40 antibody; B cell-associated molecule antibody; B-cell surface antigen CD40 antibody; Bp50 antibody; CD 40 antibody; CD40 antibody; CD40 antigen (TNF receptor superfamily member 5) antibody; CD40 antigen antibody; CD40 molecule antibody; CD40 molecule, TNF receptor superfamily member 5 antibody; CD40 protein antibody; CD40 type II isoform antibody; CD40L receptor antibody; CDw40 antibody; GP39 antibody; HIGM1 antibody; IGM antibody; IMD3 antibody; MGC9013 antibody; Nerve growth factor receptor related B lymphocyte activation molecule antibody; OTTHUMP00000031699 antibody; OTTHUMP00000031700 antibody; p50 antibody; T-BAM antibody; TBAM antibody; TNF receptor superfamily member 5 antibody; TNFRSF5 antibody; TNR5_HUMAN antibody; TRAP antibody; Tumor necrosis factor receptor superfamily , member 5 antibody; Tumor necrosis factor receptor superfamily member 5 antibody; Tumor necrosis factor receptor superfamily member 5 precursor antibody; Tumor necrosis factor receptor superfamily, member 5, isoform CRA_a antibody
Target Names
Uniprot No.

Target Background

Function
CD40 is a receptor for TNFSF5/CD40LG. It transduces signals mediated by TRAF6 and MAP3K8, activating ERK in macrophages and B cells. This leads to the induction of immunoglobulin secretion.
Gene References Into Functions
  1. CD40 plays a crucial role in the upregulation of HIF-1alpha and PTEN, contributing to the severity of microangiopathy. PMID: 29549140
  2. The CD40 rs1883832 T allele is associated with an increased susceptibility to sepsis. This association might involve the regulation of CD40 expression and plasma sCD40L levels. PMID: 29780830
  3. The 3'-UTR CD40LG (CA)n microsatellite is not a genetic marker for rheumatoid arthritis in the Western Mexican population. However, research suggests its potential role in CD40LG mRNA expression. PMID: 28963582
  4. LOAd703 is a designed adenovirus armed with trimerized CD40L and 4-1BBL, specifically designed to activate the CD40 and 4-1BB pathways. PMID: 28536305
  5. Inducible activation of MyD88 and CD40 in CAR T cells using a small-molecule drug not only enhances their effector function, resulting in potent antitumor activity in preclinical solid tumors but also enables their remote control post-infusion. PMID: 28801306
  6. The rs3765459 variant in the CD40 gene is associated with susceptibility to neuromyelitis optica spectrum disorders. PMID: 27578014
  7. Our findings suggest that several distinct susceptibility loci within CD40 may contribute to the onset and development of autoimmune thyroid diseases (AITDs). PMID: 28742400
  8. CD40 gene mutations, rs4810485 and rs1883832, have been investigated in patients with Recurrent aphthous stomatitis. PMID: 27875792
  9. miR-145-5p acts as a cardiac-protective molecule by ameliorating inflammation and apoptosis through the negative regulation of CD40 in myocardial ischemic injury. PMID: 28281187
  10. SNPs in the CD40 gene, rs4810485 G>T and rs1883832 C >T, may be associated with disease susceptibility and severity in knee osteoarthritis in the Chinese Han population. PMID: 28320398
  11. miR-145 is involved in the anti-proliferation and anti-inflammation effects of aspirin on vascular smooth muscle cells by inhibiting the expression of CD40. PMID: 27412561
  12. Selective knockdown of TNFR5 mitigates glucolipotoxic induction of STAT1 expression and NF-kappaB activity. PMID: 27512950
  13. CD40 signaling in adipose tissue macrophages regulates the expression of major histocompatibility complex class II and CD86, controlling the expansion of CD4(+) T cells. PMID: 26658005
  14. CD40 activation leads to down-regulation of Thioredoxin (Trx)-1, allowing ASK1 activation and apoptosis. While soluble receptor agonist alone cannot induce death, combined treatment with soluble CD40 agonist and pharmacological inhibition of Trx-1 replicates the signal triggered by mCD40L. PMID: 27869172
  15. Autologous CD4(+) T cells exposed to EVs from CD40/IL-4-stimulated CLL cells exhibit enhanced migration, immunological synapse signaling, and interactions with tumor cells. PMID: 27118451
  16. Simultaneous stimulation of TSHR and CD40 results in cytokine expression levels exceeding those achieved with TSH or CD40L alone. The increased expression of CD40 by TSH could be a contributing factor to this process. PMID: 27631497
  17. Glatiramer acetate treatment significantly reduces CD40-mediated P65 phosphorylation in RRMS patients. This suggests that reducing CD40-mediated p-P65 induction could be a common mechanism by which some current therapies modulate Multiple Sclerosis disease. PMID: 27798157
  18. Circulating sCD40L levels are elevated in patients with cystic fibrosis and P. aeruginosa infection. PMID: 28030642
  19. Our research indicates a significant association between rs4810485 in the CD40 gene and rs763361 in the CD226 gene polymorphism. The combined effect of rs4810485 and rs763361 is linked to an increased risk of systemic lupus erythematosus. PMID: 27722794
  20. CD40 activity in thyrocytes is primarily mediated through NF-kappaB. PMID: 27929668
  21. Polymorphisms in the TP63 and CD40 genes are associated with lung cancer in a Chinese Han population. PMID: 27063419
  22. Increased CD40 ligation and reduced B-cell receptor signaling lead to higher IL-10 production in B cells from tolerant kidney transplant recipients. PMID: 27472092
  23. Essential hypertension patients exhibit increased expression of platelet CD40. PMID: 27090943
  24. CD40 monocyte is a novel inflammatory monocyte subset that could be used as a biomarker for chronic kidney disease severity. PMID: 27992360
  25. rs1535045 in the CD40 gene is likely to be associated with Coronary Artery Disease (CAD) in the Chinese Han population. The rs4239702(C)-rs1535045(T) haplotype is associated with CAD. Patients with the rs4239702-TT genotype have higher blood lipid levels than other patients. PMID: 27200368
  26. Research suggests that CD40 SNPs rs1883832 and rs4810485 are not RA susceptibility markers in the Western Mexican population. Further studies are needed to clarify their roles in CD40 mRNA expression. PMID: 27813548
  27. Functional expression of CD40 on tumor cells could play a significant role in tumor progression and lymph node metastasis in esophageal squamous cell carcinoma. PMID: 27630283
  28. The CD40/CD40L interactions and TNF alpha are likely effective against cervical carcinomas by repressing the transcriptional activity of the human papilloma virus-18 promoter. PMID: 27031714
  29. Antigen targeting to CD40 can induce potent antigen-specific CD8(+) T cell responses in human CD40 transgenic mice. PMID: 27077111
  30. Our findings indicate that the CD40 -1C/T SNP (rs1883832) is correlated with the susceptibility to lung cancer in the Chinese population. The TT genotype may further increase the risk of lung cancer. PMID: 26823861
  31. The CD40/CD40L system plays a role in regulating bone mineral density. PMID: 26545336
  32. There were significant differences in the gene and allele frequencies of the CD40 gene rs1883832 C/T polymorphism between patients with systemic lupus erythematosus and controls. sCD40 levels were elevated in patients with SLE compared to controls. PMID: 26289938
  33. Research provides preliminary evidence that CD40 may stimulate tumor growth by enabling immune evasion through MDSC recruitment and inhibition of T cell expansion. PMID: 26462153
  34. Our results highlight novel roles for CD40 and cysteine-238-mediated CD40 homodimers in cell biology and identify a potential new target for therapeutic strategies against CD40-associated chronic inflammatory diseases. PMID: 25977307
  35. Meta-analyses confirm that the CD40 rs4810485 G/T polymorphism is associated with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Europeans. PMID: 25908480
  36. Platelet CD40 plays a crucial role in inflammation by stimulating leukocyte activation and recruitment, and activation of endothelial cells, thereby promoting atherosclerosis. PMID: 26821950
  37. The CD40 gene may play a role in the development of systemic lupus erythematosus in the Chinese population. PMID: 26474561
  38. Studies suggest that the CD40 antigen/CD154 antigen pathway represents a promising potential therapeutic target for the prevention of transplantation rejection. PMID: 26268734
  39. Research shows a multiple sclerosis (MS) risk genotype-dependent reduction of CD40 cell-surface protein in B-lymphocytes and polarized dendritic cells. MS patients, regardless of genotype, express lower levels of CD40 cell-surface protein compared to controls in B lymphocytes. Both genotype-dependent and independent downregulation of cell-surface CD40 is a feature of MS. PMID: 26068105
  40. The ability of IL21 to modulate gene and miRNA expressions in CD40-activated Chronic Lymphocytic Leukemic cells was studied. PMID: 26305332
  41. The direct CD40-CD40L interaction between breast tumor cells and activated T cells increases TGF-beta production and the differentiation of Th17 cells, promoting the proliferation of breast cancer cells. PMID: 25992978
  42. Differences in the expression levels of CD40 due to different genotypes of these two SNPs (rs4810485 and rs1883832) may contribute to the development of skin lesions or genital ulcers in patients with Behcet disease. PMID: 25373542
  43. The CD40 rs1883832C>T SNP decreases gene CD40 expression. PMID: 25600834
  44. The presence of CD40 on the T cell membrane is crucial for the induction of recombinase activity in patients with autoimmune type 1 diabetes mellitus. PMID: 22803080
  45. CD40 expression is significantly correlated with the TNM stage and the presence of distant metastasis in gastric carcinoma patients. PMID: 25665853
  46. CD40 signaling leads to sustained ERK1/2 activation and up-regulation of Bcl-xL in BCR-primed HF1A3 germinal center B cells. PMID: 26054744
  47. Subjects with the chronic hepatitis B (CHB) risk genotype TT of rs1883832 had the lowest plasma concentration of CD40, followed by subjects with CT and CC genotypes in both healthy controls and CHB patients. PMID: 25802187
  48. On the surface of B lymphocytes, the CD40 expression levels in individuals with the TT genotype were significantly lower than those with CC and CT genotypes in either the ASC group or healthy controls. PMID: 25547203
  49. A possible additive combined effect between CD40-1C>T and CTLA4+6230G>A polymorphisms in the development of Graves' disease. PMID: 25936345
  50. There is a lack of association between CD40 polymorphisms and acute rejection in German liver transplant recipients. PMID: 25305459

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Database Links

HGNC: 11919

OMIM: 109535

KEGG: hsa:958

STRING: 9606.ENSP00000361359

UniGene: Hs.472860

Involvement In Disease
Immunodeficiency with hyper-IgM 3 (HIGM3)
Subcellular Location
[Isoform I]: Cell membrane; Single-pass type I membrane protein.; [Isoform II]: Secreted.
Tissue Specificity
B-cells and in primary carcinomas.

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