CDX-1140
CDX-1140 is a fully human IgG monoclonal antibody and CD40 agonist, with a Kd value of 0.01 nM against human targets. The epitope of CDX-1140 locates at CD40 CRD1 and avoids the CD40L binding site. It activates DCs and B cells, drives NF-κB reporter gene activation, exhibits agonist activity independent of FcR cross-linking, and shows a synergistic effect with recombinant CD40L. CDX-1140 does not induce systemic cytokine release, exerts direct and immune-mediated anti-tumor activity in tumor xenografts, and has favorable safety profiles. When used as a local vaccine adjuvant in combination with 6MHP+mBRAF+poly-ICLC, CDX-1140 increases the number of DC-LAMP+ DCs and induces Th1 CD4+ responses in high-risk melanoma. CDX-1140 can be used in studies related to B-cell lymphoma, bladder cancer and high-risk melanoma.
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Activité biologique
Human
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CD40 0.01 nM (Kd) |
CDX-1140 (0.098-3.13 nM) binds human and cynomolgus macaque CD40 with high affinity (KD = 10 pM) and exhibits no cross-reactivity with other TNFR superfamily members or murine CD40[1].
CDX-1140 (0.01-10 nM; 6 day) and its F(ab′)2 fragment drive concentration-dependent proliferation of human PBMC-derived purified B cells, with ~33% and ~17% proliferation respectively at 10 nM[1].
CDX-1140 (0-10 nM; overnight) induces concentration-dependent upregulation of CD95 expression on human Ramos B cell lymphoma cells, reaching ~2400 MFI at 10 nM[1].
CDX-1140 (0.1 μg/mL; 6 day) synergizes with rCD40L (0.1 μg/mL) to induce robust proliferation of human PBMC-derived purified B cells[1].
CDX-1140 (0.001-10 nM; 6 h) and its F(ab′)2 fragment induce concentration-dependent NFκB activation in HEK-293-CD40 cells, demonstrating Fc-independent agonist activity[1].
CDX-1140 (0.01-10 nM; 48 h) drives concentration-dependent IL-12p40 production by human monocyte-derived dendritic cells, reaching ~15,000 pg/mL at 10 nM[1].
CDX-1140 (0.1 μg/mL; 48 h) synergizes with rCD40L (0.1 μg/mL) to induce high levels of IL-12p40 production by human monocyte-derived dendritic cells[1].
CDX-1140 (0.1-10 μg/mL; 24 h) does not induce significant cytokine production in human whole blood at concentrations of 0.1, 1, or 10 μg/mL across plate-bound and solution formats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human primary B cells (CD19⁺ purified from PBMC)
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Concentration:0.1 μg/mL
(Synergistic effect with rCD40L (0.1 μg/mL)) -
Incubation Time:6 days
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Result:Showed synergistic induction of B-cell proliferation (CFSE dilution), exceeding either stimulus alone, confirming the anti-CD40 mAb acts cooperatively with natural CD40L.
CDX-1140 (0.3 mg; i.p.; on days 1, 6, 13) confers significantly extended survival (p < 0.01) in SCID mice bearing subcutaneous Raji B-cell lymphoma xenografts[1].
CDX-1140 (0.3 mg; i.p.; once weekly; 3 weeks) potently inhibits tumor growth in SCID mice bearing subcutaneous EJ138 bladder carcinoma xenografts[1].
CDX-1140 (0.3 mg; i.p.; on days 1, 8, 15) synergizes with human PBMCs to confer significantly enhanced long-term survival (p < 0.001) in SCID mice bearing Ramos B-cell lymphoma xenografts[1].
CDX-1140 (0.2-2 mg/kg; i.v.; on Day 1 and Day 29) induces transient, moderate CD40-mediated pharmacodynamic effects and is well tolerated in naive cynomolgus macaques[1].
CDX-1140 (0.01-10 mg/kg; i.v.; on Days 1, 15, 29) is well tolerated in Macaca fascicularis (cynomolgus macaques), with dose-dependent CD40-mediated pharmacodynamic effects and a NOAEL of 10 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID (subcutaneous flank implantation of 0.5 × 106 Ramos human B cell lymphoma cells)[1]
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Dosage:0.3 mg
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Administration:i.p.; on days 1, 6, 13
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Result:Delayed tumor progression and extended survival compared to no treatment.
Showed significantly higher survival (p < 0.001).
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Animal Model:SCID (subcutaneous flank implantation of 1 × 106 Raji human B cell lymphoma cells)[1]
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Dosage:0.3 mg
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Administration:i.p.; on days 1, 6, 13
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Result:Delayed tumor progression and extended survival compared to no treatment.
Showed significantly higher survival (p < 0.01).
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Animal Model:SCID (subcutaneous flank implantation of 0.5 × 106 Ramos human B cell lymphoma cells mixed with 3 × 106 human PBMCs)[1]
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Dosage:0.3 mg
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Administration:i.p.; on days 1, 8, 15
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Result:Promoted complete rejection of Ramos tumors and conferred long-term survival (≥80% survival at day 90) when combined with PBMCs.
Showed significantly higher survival than no treatment, PBMCs alone, or CDX-1140 alone (p < 0.001).
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Animal Model:SCID (subcutaneous flank implantation of 1 × 106 Raji human B cell lymphoma cells mixed with 3 × 106 human PBMCs)[1]
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Dosage:0.3 mg
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Administration:i.p.; on days 1, 8, 15
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Result:Promoted complete rejection of Raji tumors and conferred 100% survival at day 90 when combined with PBMCs.
Showed significantly higher survival than no treatment, PBMCs alone, or CDX-1140 alone (p < 0.001).
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Animal Model:SCID (subcutaneous flank implantation of EJ138 human bladder carcinoma cells, mean tumor volume reached ~0.1-0.2 cm3 at treatment start)[1]
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Dosage:0.3 mg
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Administration:i.p.; once weekly; 3 weeks
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Result:Strongly inhibited tumor growth, with tumor volumes remaining near 0 cm3 through day 40.
Saline-treated mice developed large tumors (up to ~2.5 cm3 by day 40).
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Animal Model:naive (male)[1]
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Dosage:0.2 mg/kg (Day 1); 2 mg/kg (Day 29)
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Administration:i.v.; on Day 1 and Day 29
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Result:Caused transient, significant decreases in circulating B cells, white blood cells, lymphocytes, and platelets, with smaller magnitude changes compared to comparator antibody 21.4.1.
Increased serum IL-12p40 levels but lower than in 21.4.1-treated animals.
Was well tolerated with only minor serum chemistry changes.
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Animal Model:(male and female, n=10 per group except 0.01 mg/kg group with n=6)[1]
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Dosage:0.01 mg/kg; 0.1 mg/kg; 1 mg/kg; 10 mg/kg
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Administration:i.v.; on Days 1, 15, 29
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Result:Was well tolerated at all doses, with no treatment-related adverse effects in clinical signs, body weight, body temperature, or organ function.
Exhibited dose-dependent pharmacodynamic effects: at Day 2 (24 hours after first dose), doses ≥0.1 mg/kg caused significant decreases in lymphocyte and B cell counts, significant increases in serum IL-12p40, and minimal platelet decreases (median -11% at 10 mg/kg).
Effects were prolonged at the 10 mg/kg dose through Day 31.
Had a no observable adverse effect level (NOAEL) of 10 mg/kg.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Product Image
ELISA, FACS, Functional assay
Chemical Information
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N/A
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
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Fiche technique (271 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Inhibitory Antibodies User Guide (603 KB)
Références
[1]. Vitale LA, et al. Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy. Cancer immunology, immunotherapy : CII. 2019 Feb;68(2):233-245. [Content Brief]
[2]. Ninmer EK, et al. Phase I/II clinical trial of a melanoma vaccine targeting shared non-mutated antigens and a shared mutated BRAF neoantigen with an agonistic CD40 antibody (CDX-1140) plus TLR3 agonist (poly-ICLC). Journal for immunotherapy of cancer. 2026 Mar 03;14(3):e013613. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CDX-1140 Related Classifications
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