1. Apoptosis Cytoskeleton
  2. TNF Receptor Claudin
  3. Givastomig

Givastomig  (Synonyms: TJ-CD4B; ABL111; TJ033721)

Cat. No.: HY-P990742 Purity: 98.556%
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Givastomig (ABL111, TJ033721) is a bispecific antibody (BsAb) inhibitor. Givastomig can specifically binds to Claudin18.2 (CLDN 18.2) on the surface of cancer cells and 4-1BB (CD137, TNFRSF9) on the surface of activated T cells and natural killer (NK) cells. Givastomig is engineered to contain a single Fc-domain mutation (asparagine to alanine) to eliminate Fc-effector function. Givastomig-bound cell lines expressing a range of CLDN18.2 levels with high affinity and induced 4-1BB activation only in the context of CLDN18.2 binding. Givastomig can be used for the study of colon carcinoma.

For research use only. We do not sell to patients.

CAS No. : 2762499-30-7

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Based on 1 publication(s) in Google Scholar

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Description

Givastomig (ABL111, TJ033721) is a bispecific antibody (BsAb) inhibitor. Givastomig can specifically binds to Claudin18.2 (CLDN 18.2) on the surface of cancer cells and 4-1BB (CD137, TNFRSF9) on the surface of activated T cells and natural killer (NK) cells. Givastomig is engineered to contain a single Fc-domain mutation (asparagine to alanine) to eliminate Fc-effector function. Givastomig-bound cell lines expressing a range of CLDN18.2 levels with high affinity and induced 4-1BB activation only in the context of CLDN18.2 binding. Givastomig can be used for the study of colon carcinoma[1].

Isotype

IgG1-kappa-[scFv-lambda-heavy]2

Recommend Isotype Controls
Species Reactivity

Human

IC50 & Target

TNFRSF9 & CLDN18

In Vitro

Givastomig binds to human CLDN18.2 VLP and human 4-1BB protein with high affinity, achieving an equilibrium dissociation constant (KD = 1.698 × 10-10/9.88 × 10-9 M)[1].
Givastomig (0.001-1000 nM, 1 h) specifically binds to CLDN18.2 (EC50 = 0.13 nM) and does not cross-react with its isoform CLDN18.1 expressed in normal lung tissue[1].
Givastomig (0.001-1000 nM, 30 min) shows a stronger binding affinity to all the tested CHO-K1-hCLDN18.2 expressing high, medium and even low level of CLDN18.2 than the control monoclonal antibody[1].
Givastomig (6 h) is co-cultured with NF-κB/4-1BB reporter Jurkat cell lines, which induces strong NF-κB signaling activation, while when co-cultured with CLDN18.2+ cells, it does not activate NF-κB signaling[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Givastomig (4 mg/kg, i.v., Biweekly) conditionally activates 4-1BB+ T cells in the tumor microenvironment by targeting CLDN18.2-positive tumor cells, thereby generating a potent anti-tumor immune response and durable immune memory in mouse models[1].
Givastomig (0.4-10 mg/kg, i.v., once a week, for a total of three cycles) shows that the anti-tumor activity in colon carcinoma mouse models is dose-dependent[1].
Givastomig (10-100 mg/kg, i.v., once a week, for 5 times) demonstrates excellent safety in cynomolgus monkeys[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female C57BL/6-Tnfrsf9tm1 (TNFRSF9) (humanized h4-1BB) mice at the age of 6-8 weeks were subcutaneously inoculated with human CLDN18.2 expressing MC38 (MC38hCLDN18.2) colon carcinoma tumor cells (5×105 cells)[1].
Dosage: 4 mg/kg
Administration: I.v., Biweekly
Result: The tumor almost completely disappeared.
Fifty-four days after the initial tumor inoculation, cured mice were challenged again with MC38hCLDN18.2 tumor cells. All cured mice developed resistance to the new tumor challenge, while untreated juvenile mice developed tumors.
The tumor infiltration of CD45+ leukocytes and CD8+ T cells was significantly increased, and the CD8+/Treg (regulatory T cell) ratio was improved.
Animal Model: Female C57BL/6-Tnfrsf9tm1 (TNFRSF9) (humanized h4-1BB) mice at the age of 6-8 weeks were subcutaneously inoculated with human CLDN18.2 expressing MC38 (MC38hCLDN18.2) colon carcinoma tumor cells (5×105 cells)[1].
Dosage: 0.4 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, 10 mg/kg
Administration: I.v., once a week, for a total of three cycles
Result: The antitumor activity is dose-dependent. Low doses (0.4, 1 mg/kg) produce partial efficacy, while high doses (5, 10 mg/kg) achieve complete tumor regression.
The increase in intratumoral CD45+ leukocytes and CD8+ T cells is positively correlated with the administered dose.
Animal Model: Cynomolgus monkeys (Macaca fascicularis)[1].
Dosage: 10 mg/kg, 30 mg/kg, 100 mg/kg
Administration: I.v., once a week, for 5 times
Result: The drug was well tolerated at doses up to 100 mg/kg, with no observed adverse event level (NOAEL).
No drug-related hepatotoxicity was observed.
Peripheral blood immune cell typing and cytokine testing 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.
Clinical Trial
Gene ID

3604  [NCBI] & 51208  [NCBI]

Accession
Application

ELISA, FACS, Functional assay

Conjugated

Unconjugated

Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.

Molecular Weight

201.929 kDa

CAS No.
Appearance

Liquid

Color

Colorless to light yellow

Shipping

Shipping with dry ice.

Formulation

Please refer to the lot-specific COA for specific buffer information.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Format
  • IgG1-kappa-[scFv]2-lambda-heavy
Biological Activity
  • Immobilized 4-1BB/TNFRSF9 Protein, Human (HY-P7125) can bind Givastomig. The EC50 for this effect is 1.795 ng/mL.
  • Immobilized Claudin-18/CLDN18.2 Protein-VLP, Human (HEK293, HY-P78368) can bind Givastomig. The EC50 for this effect is 1.744 ng/mL.
Purity & Documentation
References
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Givastomig
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HY-P990742
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