Anti-mGITR-mIgG2a InvivoFit™
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Cat.code:
mgitr-mab10-1
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ABOUT
Recombinant murinized GITR antibody for in vivo use
Anti-mGITR-mIgG2a InvivoFit™ is a recombinant murinized anti-mouse monoclonal antibody (mAb) featuring the variable region of the previously described anti-mGITR clone DTA-1 [1]. The rat-derived constant region was replaced by a murine constant region, making the mAb ~65% of murine origin. This feature allows for reduced immunogenicity and risks of fatal hypersensitivity reactions upon repeated mAb injections into mice [2-4]. Anti-mGITR-mIgG2a is provided in an InvivoFit™ grade, a high-quality standard specifically adapted to in vivo studies.
This agonist mAb has been reported to increase T cell and NK cell activity, cytotoxicity, and degranulation in vivo [4]. It shows strong antitumor efficacy by modulating both effector (Teffs) and regulatory (Tregs) T cells [4-5]. The Anti-mGITR mAb efficacy is moderate on its own; thus, it is more often used in combination with other immune checkpoint mAbs (e.g. CTLA4, PD-1) [4]. Notably, the anti-GITR (DTA-1) antibody seems to trigger anaphylaxis in C57BL/6 mice in a target/isotype-dependent manner [4]. Thus, the correct selection of a strain-matched heavy chain isotype prior to in vivo experiments is crucial (IgG2a for Balb/c, swiss mice & IgG2c for C57BL/6 mice). If you are interested in an Anti-mGITR-mIgG2c, please contact us
Key features of Anti-mGITR-mIgG2a InvivoFit™:
- Specific binding to mouse GITR
- Features the IgG2a isotype (associated with high antitumor activity)
- Filter-sterilized (0.2 µm), endotoxin level < 1 EU/mg
- Specifically designed for in vivo studies in mice
- Produced in animal-free facilities and defined media
- Low aggregation < 5%
GITR (Glucocorticoid-Induced TNFR-Related protein) is a co-stimulatory immune checkpoint protein found on a variety of immune cells, including T cells, natural killer (NK) cells, and some myeloid cells. The interaction of GITR with its ligand GITRL can modulate the pathogenesis of tumors, inflammation, and autoimmune diseases [5].
References:
1. Cohen AD, et al., 2010. Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS One.;5(5):e10436.
2. Mall C. et al., 2016. Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogenic hypersensitivity reactions in a murine model of breast cancer. Onco Immunol. 5(2):e1075114.
3. Murphy, J.T. et al., 2014. Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice. Blood. 123(14):2172-2180.
4. Belmar N.A. et al., 2017. Murinization and H chain isotype matching of Anti-GITR antibody DTA-1 reduces immunogenicity-mediated anaphylaxis in C57BL/6 mice. J Immunol. 198:4502-4512.
5. Tian J, et al., 2020. The Role of GITR/GITRL Interaction in Autoimmune Diseases. Front Immunol.;11:588682.
All products are for research use only, and not for human or veterinary use.
InvivoFit™
InvivoFit™ is a high-quality standard specifically adapted for in vivo studies.
InvivoFit™ products are filter-sterilized (0.22 µm) and filled under strict aseptic conditions in a clean room. The level of bacterial contaminants (endotoxins and lipoproteins) in each lot is verified using a LAL assay and a TLR2 and TLR4 reporter assay
SPECIFICATIONS
Specifications
GITR
Mouse
No cross-reactivity with human GITR
In vivo studies, ELISA, flow cytometry
Sodium phosphate buffer, saccharose
< 5%
0.2 µm filtration
Endotoxin level <1 EU/mg (determined by the LAL assay)
ELISA
Each lot is functionally tested by ELISA.
CONTENTS
Contents
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Product:Anti-mGITR-mIgG2a InvivoFit™
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Cat code:mgitr-mab10-1
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Quantity:1 mg
Shipping & Storage
- Shipping method: Room temperature
- -20 °C
- Avoid repeated freeze-thaw cycles
Storage:
Caution:
Details
GITR
The glucocorticoid-induced TNF receptor–related protein GITR (also known as CD357 or TNFRSF18) is an immune receptor that belongs to Tumor Necrosis Factor Receptor Superfamily (TNFRSF). The engagement with its ligand GITRL (TNFSF18, AITRL, CD357L) has been shown to modulate both the acquired and innate immune system [1]. GITR is mainly expressed on activated CD4+, CD8+, and FoxP3+ T cells. To a lesser extent, it is also found on natural killer (NK) cells, B cells, mast cells, and keratinocytes. The ligand GITRL is primarily found in various APCs, including dendritic cells (DCs) subsets, B cells, monocytes, endothelial cells, and interestingly in human tumor cells [2].
Given the divers expression patterns, the GITR/GITRL axis may play a role not only in regulating immune responses but also in mediating leukocyte adhesion and migration [3]. Indeed, GITR activation and function is cell type and context dependent, and therefore can have divers effects [3].
GITR signaling
GITR signaling is mediated through the TRAF (TNF receptor-associated factors )-dependent activation of NF-κB as well as members of the MAPK pathway, including ERK, p38 and JNK [1,3]. On activated CD8+ effector T cells (Teffs), GITR has a co-stimulatory function by enhancing cell activation, cytokine secretion, proliferation, and survival [3]. In contrast, GITR activation on murine regulatory T cells (Tregs) abrogates their suppressive function on Teffs leading to increased Teffs survival and therefore, enhanding antitumor responses [3]. In vivo data suggests, that GITR signaling is involved in the development of autoimmune diseases, graft-versus-host disease, and in the immune response against infectious pathogens. Moreover, in murine tumor models, GITR modulation has been reported to influence animal survival and even lead to the eradication of tumors [4]. However, several studies show severe differences of GITR/GITRL between human and mice regarding expression profile, signaling and structure [4,5]. Therefore, additional studies are required to elucidate the possible differences between GITR/GITRL-modulating reagents in human and mice [5].
References:
1. Tian J, et al., 2020. The Role of GITR/GITRL Interaction in Autoimmune Diseases. Front Immunol.;11:588682.
2. Nocentini G, Riccardi C., 2009. GITR: a modulator of immune response and inflammation. Adv Exp Med Biol. 2009;647:156-73.
3. Knee DA, et al,. 2016. Rationale for anti-GITR cancer immunotherapy. Eur J Cancer.;67:1-10.
4. Baltz KM, et al., 2008. Neutralization of tumor-derived soluble glucocorticoid-induced TNFR-related protein ligand increases NK cell anti-tumor reactivity. Blood. 2008 Nov 1;112(9):3735-43.
5. Baltz KM, et al., 2007. Cancer immunoediting by GITR (glucocorticoid-induced TNF-related protein) ligand in humans: NK cell/tumor cell interactions. FASEB J.;21(10):2442-54.
6. Wang, F. et al., 2021. Structures of mouse and human GITR–GITRL complexes reveal unique TNF superfamily interactions. Nat Commun 12, 1378.
DOCUMENTS
Documents
Technical Data Sheet
Validation Data Sheet
Safety Data Sheet
Certificate of analysis
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