InVivoSIM anti-human CTLA-4 (Ipilimumab Biosimilar)

Catalog #SIM0004
Clone:
Ipilimumab
Reactivities:
Human

$217.00 - $7,526.00

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Product Details

This non-therapeutic biosimilar antibody uses the same variable regions from the therapeutic antibody Ipilimumab making it ideal for research use. This Ipilimumab biosimilar reacts with human CTLA-4 (cytotoxic T lymphocyte antigen-4) also known as CD152. CTLA-4 is a 33 kDa cell surface receptor encoded by the Ctla4 gene that belongs to the CD28 family of the Ig superfamily. CTLA-4 is expressed on activated T and B lymphocytes. CTLA-4 is structurally similar to the T-cell co-stimulatory protein, CD28, and both molecules bind to the B7 family members B7-1 (CD80) and B7-2 (CD86). Upon ligand binding, CTLA-4 negatively regulates cell-mediated immune responses. CTLA-4 plays roles in induction and/or maintenance of immunological tolerance, thymocyte development, and regulation of protective immunity. CTLA-4 is among a group of inhibitory receptors being used as cancer treatment targets through immune checkpoint blockade. Ipilimumab binds to CTLA-4, blocking the inhibitory signal, which allows the cytotoxic T cells to kill cancer cells.

Specifications

Isotype Human IgG1
Recommended Isotype Control(s) RecombiMAb human IgG1 isotype control, anti-hen egg lysozyme
Recommended Dilution Buffer InVivoPure pH 7.0 Dilution Buffer
Immunogen Human CTLA-4
Reported Applications CTLA-4 neutralization
Flow Cytometry
ELISA
Western Blot
Formulation PBS, pH 7.0
Contains no stabilizers or preservatives
Endotoxin <1EU/mg (<0.001EU/μg)
Determined by LAL gel clotting assay
Aggregation <5%
Determined by SEC
Purity >95%
Determined by SDS-PAGE
Sterility 0.2 µm filtration
Production Purified from cell culture supernatant
Purification Protein A
RRID AB_2894725
Molecular Weight 150 kDa
Murine Pathogen Tests Ectromelia/Mousepox Virus: Negative
Hantavirus: Negative
K Virus: Negative
Lactate Dehydrogenase-Elevating Virus: Negative
Lymphocytic Choriomeningitis virus: Negative
Mouse Adenovirus: Negative
Mouse Cytomegalovirus: Negative
Mouse Hepatitis Virus: Negative
Mouse Minute Virus: Negative
Mouse Norovirus: Negative
Mouse Parvovirus: Negative
Mouse Rotavirus: Negative
Mycoplasma Pulmonis: Negative
Pneumonia Virus of Mice: Negative
Polyoma Virus: Negative
Reovirus Screen: Negative
Sendai Virus: Negative
Theiler’s Murine Encephalomyelitis: Negative
Storage The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.
in vivo CTLA-4 neutralization
Crupi MJF, Taha Z, Janssen TJA, Petryk J, Boulton S, Alluqmani N, Jirovec A, Kassas O, Khan ST, Vallati S, Lee E, Huang BZ, Huh M, Pikor L, He X, Marius R, Austin B, Duong J, Pelin A, Neault S, Azad T, Breitbach CJ, Stojdl DF, Burgess MF, McComb S, Auer R, Diallo JS, Ilkow CS, Bell JC. (2022). "Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer" Front Immunol 13:1029269. PubMed

Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer mortality worldwide, highlighting an urgent need for new therapeutic options and combination strategies for patients. The orchestration of potent T cell responses against human cancers is necessary for effective antitumour immunity. However, regression of a limited number of cancers has been induced by immune checkpoint inhibitors, T cell engagers (TCEs) and/or oncolytic viruses. Although one TCE has been FDA-approved for the treatment of hematological malignancies, many challenges exist for the treatment of solid cancers. Here, we show that TCEs targeting CEACAM5 and CD3 stimulate robust activation of CD4 and CD8-positive T cells in in vitro co-culture models with colorectal cancer cells, but in vivo efficacy is hindered by a lack of TCE retention in the tumour microenvironment and short TCE half-life, as demonstrated by HiBiT bioluminescent TCE-tagging technology. To overcome these limitations, we engineered Bispecific Engager Viruses, or BEVirs, a novel tumour-targeted vaccinia virus platform for intra-tumour delivery of these immunomodulatory molecules. We characterized virus-mediated TCE-secretion, TCE specificity and functionality from infected colorectal cancer cells and patient tumour samples, as well as TCE cytotoxicity in spheroid models, in the presence and absence of T cells. Importantly, we show regression of colorectal tumours in both syngeneic and xenograft mouse models. Our data suggest that a different profile of cytokines may contribute to the pro-inflammatory and immune effects driven by T cells in the tumour microenvironment to provide long-lasting immunity and abscopal effects. We establish combination regimens with immune checkpoint inhibitors for aggressive colorectal peritoneal metastases. We also observe a significant reduction in lung metastases of colorectal tumours through intravenous delivery of our oncolytic virus driven T-cell based combination immunotherapy to target colorectal tumours and FAP-positive stromal cells or CTLA4-positive Treg cells in the tumour microenvironment. In summary, we devised a novel combination strategy for the treatment of colorectal cancers using oncolytic vaccinia virus to enhance immune-payload delivery and boost T cell responses within tumours.