2141-V11
Based on 1 Customer Validation
2141-V11 is an Fc-engineered agonistic antibody against human CD40 with selectively enhanced binding affinity for human FcγRIIB. 2141-V11 drives CD40 multimerization and agonistic signal transduction, activates dendritic cells, promotes antigen cross-presentation and CD8+ T cell priming, induces tertiary lymphoid structure formation, increases leukocyte infiltration, and mediates local and abscopal anti-tumor effects, systemic immune activation and immune memory. 2141-V11 exhibits extremely low systemic toxicity upon intratumoral or intravesical administration, with no dose-limiting toxicity observed at the tested intratumoral doses, whereas high-dose systemic administration induces thrombocytopenia and elevated transaminases. 2141-V11 can be used in research related to breast cancer, melanoma, BCG-unresponsive non-muscle invasive bladder cancer, and recurrent malignant glioma.
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- Purity: 99.04%
- CAS No.: 2923542-55-4
- 분자량:146.80 kDa
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
Human IgG1 kappa
Human
2141-V11 (0.2 mg/kg; i.t.; 4 doses on days 14, 17, 21, and 24; administered to one tumor only) drives abscopal antitumor effects in bilateral E0771 breast tumors in hCD40/hFcγR mice and promotes de novo mature TLS formation exclusively in injected tumors[1].
2141-V11 (0.2 mg/kg; i.t.; 4 doses on days 14, 17, 21, and 24; administered to one tumor only) mediates local tumor rejection in bilateral E0771 breast tumors independent of lymph node immune egress, while systemic abscopal effects require immune cell trafficking from lymph nodes, and induces systemic CD8+ T cell clonal expansion and pro-inflammatory cytokine production[1].
2141-V11 (intravesical) promotes tertiary lymphoid structure formation in orthotopic MB49 bladder tumors in hCD40/hFcγR mice[1].
2141-V11 (0.01-0.1 mg/kg; intratumoral; four doses on days 8, 10, 12, 14 post-tumor implantation) provides durable, systemic antitumor immunity with minimal toxicity, while systemic administration at the maximum tolerated dose (0.1 mg/kg; i.p.; four doses on days 7, 11, 15, 18 post-tumor implantation) achieves superior tumor control to the parental antibody without overt toxicity[2].
2141-V11 (3-100 mg/kg/dose; s.c., i.v.; 2 doses on days 1 and 22) is well-tolerated in healthy cynomolgus monkeys, with no observed major toxicities and expected pharmacokinetic profiles[1].
2141-V11 (0.03125-0.5 mg/kg; single dose) causes dose-dependent liver toxicity and thrombocytopenia in humanized hFcγR/hCD40 mice, with a maximum tolerated dose of 0.1 mg/kg[2].
2141-V11 (0.1 mg/kg; intratumoral; four doses on days 8, 10, 12, 14 post-tumor implantation) expands antigen-specific CD8 T cells in the periphery in a CD8 T-cell-dependent, macrophage-independent manner[2].
2141-V11 (0.1 mg/kg; intratumoral; four doses on days 8, 10, 12, 14 post-tumor implantation) controls aggressive B16 melanoma and synergizes with systemic PD-1 blockade to enhance antitumor activity[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:hCD40/hFcγR mice (humanized for CD40 and all human FcγRs)[1]
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Dosage:0.2 mg/kg
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Administration:i.t.; 4 doses on days 14, 17, 21, and 24
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Result:Induced complete tumor regression in all treated mice by day 35.
Fully protected primed mice from tumor rechallenge, with no tumor growth observed.
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Animal Model:hCD40/hFcγR mice (humanized for CD40 and all human FcγRs)[1]
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Dosage:0.2 mg/kg
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Administration:i.t.; 4 doses on days 14, 17, 21, and 24; administered to one tumor only
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Result:Induced regression of both injected and non-injected bilateral E0771 tumors.
Detected mature tertiary lymphoid structures (TLS) in 5/6 injected tumors, characterized by B220+ B cells, CD4+ and CD8+ T cells, CD11c+ DCs, and elevated CD21 and podoplanin expression.
Observed no TLS in non-injected tumors (0/6) or control tumors (0/6).\nDid not impair local tumor rejection of injected tumors when combined with FTY720, but FTY720 completely abrogated the antitumor effect in non-injected tumors.
Induced expansion of proliferating and effector CD8+ T cells in injected tumors, with substantial clonal overlap of effector CD8+ T cells between injected and non-injected tumors.
Increased serum levels of IFN-γ, IL-15, IL-18, CXCL10, CCL7, and CXCL13 after the second dose.
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Animal Model:Cynomolgus monkeys[1]
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Dosage:3 mg/kg/dose (s.c.); 3 mg/kg/dose (i.v.); 100 mg/kg/dose (s.c.)
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Administration:s.c.; 2 doses on days 1 and 22; i.v.; 2 doses on days 1 and 22
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Result:Observed no major adverse events, unscheduled deaths, body weight changes, clinical symptoms, or local reactions.
Kept liver enzymes (AST, ALT) and platelet counts stable.
Showed expected time-concentration serum profiles, with peak levels between 24 and 72 hours.
Reached maximum tolerated dose of 3 mg/kg/dose (i.v.) and 100 mg/kg/dose (s.c.).
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Animal Model:Humanized hFcγR/hCD40 mice (8-12 weeks old, MC38 colorectal carcinoma tumor implanted subcutaneously into bilateral flanks)[2]
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Dosage:0.1 mg/kg (i.p.); 0.01 mg/kg (intratumoral); 0.1 mg/kg (intratumoral)
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Administration:i.p.; four doses on days 7, 11, 15, 18 post-tumor implantation; intratumoral; four doses on days 8, 10, 12, 14 post-tumor implantation
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Result:Achieved significantly better tumor control than the parental 2141-IgG2 antibody, with no evidence of liver toxicity (AST/ALT levels similar to untreated controls) or thrombocytopenia at study end point.
Resulted in significantly lower tumor burden at injected and non-injected tumor sites compared to systemic delivery and control groups, with no liver or platelet toxicity.
A significant fraction of mice demonstrated long-term survival, and nearly all cured mice were protected from rechallenge with 10× the initial tumor cell dose.
Induced rapid, durable control of both injected and distant tumor sites; this activity was completely abrogated by CD8 T-cell depletion, but not by CD4 T-cell, macrophage, or NK-cell depletion.
The activity was Fc-receptor dependent, as a non-Fc-binding variant (2141-N297A) showed no tumor growth inhibition.
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Animal Model:Humanized hFcγR/hCD40 mice (MC38/OVA ovalbumin-expressing colorectal carcinoma tumor implanted subcutaneously)[2]
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Dosage:0.1 mg/kg
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Administration:intratumoral; four doses on days 8, 10, 12, 14 post-tumor implantation
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Result:Induced a statistically significant expansion of ovalbumin-specific CD8 T cells in the peripheral blood of treated mice; this expansion was eliminated by CD8 T-cell depletion but not affected by macrophage depletion.
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Animal Model:Humanized hFcγR/hCD40 mice (B16 melanoma tumor implanted subcutaneously into bilateral flanks)[2]
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Dosage:0.1 mg/kg
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Administration:intratumoral; four doses on days 8, 10, 12, 14 post-tumor implantation
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Result:Alone achieved rapid, persistent control of injected B16 tumors, while systemic single-agent PD-1 blockade had no significant effect on tumor growth.
Combination therapy with intratumoral 2141-V11 and systemic PD-1 blockade led to significantly improved control of both injected and non-injected tumors in all treated mice, with minimal off-target toxicity.
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Animal Model:Humanized hFcγR/hCD40 mice (healthy, no tumor implantation)[3]
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Dosage:0.03125 mg/kg; 0.125 mg/kg; 0.25 mg/kg; 0.5 mg/kg
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Administration:single dose
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Result:Was well tolerated at doses up to 0.1 mg/kg.
At doses ≥0.25 mg/kg, caused profound transaminitis (elevated AST/ALT levels), intravascular liver thrombi, and hepatocyte necrosis.
No hepatic toxicity was observed at 0.125 mg/kg or lower.
Increasing doses led to worsening thrombocytopenia, with no significant effect on other blood count parameters.
The maximum tolerated dose (MTD) was determined to be 0.1 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.
ELISA, FACS, Functional assay
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Immobilized hu-CD40-his can bind 2141-V11. The EC50 for this effect is 17.38 ng/mL.
Chemical Information
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CAS No. 2923542-55-4
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Appearance Liquid
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분자량 146.80 kDa
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Color Colorless to light yellow
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SMILES
N/A
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선적
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
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Data Sheet (272 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
References
[1]. Osorio JC, et al. Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer. Cancer cell. 2025 Oct 13;43(10):1902-1916.e9. [Content Brief]
[2]. Knorr DA, et al. Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. Proceedings of the National Academy of Sciences of the United States of America. 2018 Oct 23;115(43):11048-11053. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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