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| 1mg |
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| Other Sizes |
| Targets |
PD-1 (Programmed death-1) and IL-21R (Interleukin-21 receptor) are the two targets of Latikafusp. The PD-1-targeting antibody component of the fusion protein binds to PD-1 on immune cells, blocking the PD-1/PD-L1 interaction and preventing inhibitory signal transduction. Simultaneously, the IL-21 mutein component delivers IL-21 pathway stimulation specifically to PD-1+ cells. IL-21 is a cytokine that promotes the proliferation and persistence of cytotoxic and memory T cells. By targeting IL-21 stimulation to PD-1+ cells, Latikafusp enhances the priming and persistence of cytotoxic and memory T cells while avoiding systemic cytokine toxicity.
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| ln Vitro |
In vitro, Latikafusp blocks PD-1 signaling while simultaneously providing IL-21 pathway stimulation to PD-1+ cells. It enhances the priming and persistence of cytotoxic and memory T cells. The fusion protein promotes T cell proliferation, increases the secretion of IFN-γ and other pro-inflammatory cytokines, and enhances the cytotoxic activity of T cells against tumor cells. The dual mechanism of action of Latikafusp results in superior T cell activation compared to PD-1 blockade alone.
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| ln Vivo |
In vivo, Latikafusp induces anti-tumor immunity and demonstrates antitumor activity in preclinical models. It is being investigated in clinical trials for advanced solid tumors. The targeted delivery of IL-21 stimulation to PD-1+ cells results in enhanced antitumor efficacy with reduced systemic toxicity compared to systemic IL-21 administration. The fusion protein has shown promising results in preclinical studies, supporting its continued development as an immunotherapeutic agent.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for Latikafusp involves binding assays to measure the affinity of the PD-1-targeting antibody component to PD-1. PD-1 is immobilized on a sensor chip or microplate, and various concentrations of Latikafusp are incubated to determine the equilibrium dissociation constant (Kd). Functional assays assess IL-21 receptor activation and downstream signaling in PD-1+ cells, including STAT3 phosphorylation and other signaling pathway readouts.
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| Cell Assay |
In vitro cellular assays for Latikafusp use PD-1+ T cells treated with the fusion protein. T cell activation and proliferation assays are performed to evaluate the bifunctional activity of the fusion protein. Cytokine production (IFN-γ, TNF-α, IL-2), proliferation (CFSE dilution or [³H]-thymidine incorporation), and cytotoxicity against tumor cells are measured. The ability of Latikafusp to enhance the priming and persistence of memory T cells is also assessed in long-term culture assays.
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| Animal Protocol |
In vivo animal experiments for Latikafusp are conducted in mouse tumor models to assess antitumor efficacy. Tumor growth inhibition, immune cell infiltration, and survival are measured following administration. Immunocompetent mice bearing syngeneic tumors are used to evaluate the antitumor activity of the fusion protein. Latikafusp is administered via intraperitoneal (IP) or intravenous (IV) injection at various dose levels. Tumor growth inhibition is assessed by measuring tumor volumes over time. Immune cell infiltration into tumors is evaluated by immunohistochemistry for CD8+ T cells and other immune markers.
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| ADME/Pharmacokinetics |
Pharmacokinetics of Latikafusp (AMG 256) are being evaluated in a Phase 1 study in patients with advanced solid tumors. As a bifunctional fusion protein, Latikafusp is expected to exhibit pharmacokinetic properties consistent with other antibody-based therapeutics, including a long half-life and low clearance. The PK profile supports dosing intervals appropriate for antibody-based therapies.
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| Toxicity/Toxicokinetics |
Safety and tolerability of Latikafusp are being evaluated in a Phase 1 dose-escalation study to determine the maximum tolerated dose and recommended Phase 2 dose. Latikafusp may lead to the development of immunogenicity-mediated responses. As a fusion protein combining checkpoint inhibition with cytokine stimulation, Latikafusp may have a unique safety profile that requires careful monitoring for immune-related adverse events and cytokine-related toxicities.
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| References |
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| Additional Infomation |
Latikafusp (AMG 256) is a novel bifunctional fusion protein being developed for the treatment of solid tumors. It is currently in Phase 1 clinical development. The fusion protein combines a PD-1-targeting antibody with an IL-21 mutein, providing targeted IL-21 pathway stimulation to PD-1+ cells. Latikafusp is not approved by any regulatory authority and is not commercially available. The CAS number for Latikafusp is 2552814-07-8. The fusion protein is intended for research purposes only and is not for human use outside of clinical trials.
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| CAS # |
2552814-07-8
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| Appearance |
Colorless to light yellow liquid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
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