| ln Vitro |
Givastomig has a high affinity for human CLDN18.2 VLP and human 4-1BB protein, reaching an equilibrium dissociation constant (KD = 1.698 × 10⁻¹⁰/9.88 × 10⁻⁹ M)[1]. Givastomig (0.001–1000 nM, 1 hour) specifically binds to CLDN18.2 (EC50 = 0.13 nM) and does not cross-react with the CLDN18.1 isoform expressed in normal lung tissue[1]. Givastomig (0.001–1000 nM, 30 minutes) showed stronger binding affinity to all tested CHO-K1-hCLDN18.2 cells (regardless of high, medium, or low CLDN18.2 expression levels) than the control monoclonal antibody[1]. Givastomig (6 h) co-cultured with the NF-κB/4-1BB reporter gene Jurkat cell line can induce strong NF-κB signal activation, while co-cultured with CLDN18.2+ cells will not activate NF-κB signal [1].
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| ln Vivo |
Givastomig (4 mg/kg, intravenously every two weeks) conditionally activates 4-1BB+ T cells in the tumor microenvironment by targeting CLDN18.2-positive tumor cells, thereby generating a potent antitumor immune response and durable immune memory in mouse models [1]. Givastomig (0.4–10 mg/kg, intravenously once a week for three cycles) showed dose-dependent antitumor activity in a mouse model of colon cancer [1]. Givastomig (10–100 mg/kg, intravenously once a week for five cycles) showed good safety in cynomolgus monkeys [1].
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| Animal Protocol |
Animal/Disease Models:Subcutaneous inoculation of MC38 (MC38hCLDN18.2) colon cancer cells expressing human CLDN18.2 (5 × 10⁵ cells) into 6-8 week old female C57BL/6-Tnfrsf9tm1 (TNFRSF9) (humanized h4-1BB) mice[1].
Doses: 4 mg/kg Route of Administration: Intravenous injection every two weeks Experimental Results: Tumors almost completely disappeared. 54 days after the first tumor inoculation, the cured mice were re-inoculated with MC38hCLDN18.2 tumor cells. All cured mice developed resistance to new tumor attacks, while untreated young mice developed tumors. Tumor infiltration of CD45+ leukocytes and CD8+ T cells was significantly increased, and the CD8+/Treg (regulatory T cell) ratio was improved. Animal/Disease Models:Subcutaneous inoculation of MC38 (MC38hCLDN18.2) colon cancer cells expressing human CLDN18.2 (5 × 10⁵ cells) into 6-8 week old female C57BL/6-Tnfrsf9tm1 (TNFRSF9) (humanized h4-1BB) mice[1]. Doses: 0.4 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, 10 mg/kg. Route of Administration: Intravenous injection, once a week for three cycles. Experimental Results: Antitumor activity was dose-dependent. Low doses (0.4, 1 mg/kg) produced partial efficacy, while high doses (5, 10 mg/kg) achieved complete tumor regression. The increase in CD45+ leukocytes and CD8+ T cells in the tumor was positively correlated with the dose. Animal/Disease Models:Crab-eating macaque (Macaca fascicularis) [1]. Doses: 10 mg/kg, 30 mg/kg, 100 mg/kg. Route of Administration: Intravenous injection, once a week for a total of 5 weeks. Experimental Results: The drug was well tolerated at doses up to 100 mg/kg, and no adverse event level (NOAEL) was observed. No drug-related hepatotoxicity was observed. Peripheral blood immune cell typing and cytokine detection showed no signs of systemic immune activation. Monitoring of body weight, food consumption, clinical symptoms, electrocardiogram, hematology, and coagulation function revealed no drug-induced abnormalities. |
| References |
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| CAS # |
2762499-30-7
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|---|---|
| Related CAS # |
Cell-ATP Viability Detection Kit; Protein A Agarose; HOLO Human Interleukin-2 (IL-2) Detection Kit; Bradford Protein Assay Kit; Cell Counting Kit-8
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| Appearance |
Colorless to light yellow liquid
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| Synonyms |
TJ-CD4B; ABL111; TJ033721
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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.
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