Anti-mPD-1-mIgG1e3 (4C11)
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Cat.code:
mpd1c2-mab15-1
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ABOUT
Recombinant mouse PD-1 antibodies in InvivoFit™ grade
InvivoGen offers fully mouse antibodies targeting the mouse (m)PD-1 (programmed cell death ligand 1) in two formats:
- Anti-mPD-1-mIgG1e3 (4C11) featuring a mutated (D265A) mIgG1 constant region
for no effector functions.
- Anti-mPD-1-mIgG1 (4C11) featuring a native mIgG1 constant region.
Both monoclonal antibodies (mAbs) are 100% murine, as the original clone 4C11 was raised in PD-1 knockout mice using a proprietary method, designed to overcome the limitation of using xenogeneic mAbs in vivo.
In contrast, the original RMP1-14 clone, widely used in PD-1 pathway studies, was developed in rats by immunizing with mPD-1-expressing cells [1]. Repeated administrations of such rat-derived mAbs often trigger host anti-rat immune responses, which can compromise antibody performance or lead to immunogenic events [2-3]. Indeed, in a syngeneic tumor mouse model, treatment with the 100% murine Anti-mPD1-mIgG1e3 (4C11) clone resulted in improved survival and tumor regression compared to the RMP1-14 clone (see figures). The 4C11 clone achieved a higher rate of tumor-free mice (4/9 vs. 1/9) and delayed tumor progression more effectively.
In the Fc region of Anti-mPD-1-mIgG1e3 (4C11) InvivoFit™, a point mutation was introduced, changing the aspartic (D) acid at position 265 to an alanine (A) (D265A). This alteration abolished any unwanted Fc-mediated effector functions, ensuring a more controlled and specific PD-1 pathway blockage [4]. Together, these design characteristics make the 4C11-derived mAbs ideally suited for in vivo studies, enhancing both safety and experimental reproducibility [3].
Key features
- Each lot is functionally tested and validated
- The complete sequence of the antibody construct was verified.
- Low aggregation < 5%
- InvivoFit™ grade: specifically designed for in vivo studies in mice
Applications
- In vivo experiments
- Fc-mediated effector function studies
- Comparable studies using different anti-mPD-1 mAbs
Programmed cell death ligand 1 (PD-L1; also called B7-H1 or CD274) binds to programmed cell death protein 1 (PD-1) on T cells and contributes to T cell exhaustion during chronic infections. Moreover, the engagement of PD-1 on T cells and PD-L1 on malignant cells is associated with the immune escape of tumors. Clinical trials have highlighted the anti-tumor efficacy of blockades targeting the PD-1/PD-L1 pathway [5].
References:
1. Yamazaki T. et al.,2005. Blockade of B7-H1 on macrophages suppresses CD4+ T cell proliferation by augmenting IFN-gamma-induced nitric oxide production. J Immunol. 175(3):1586-92.
2. Brüggemann M. et al., 1989. The immunogenicity of chimeric antibodies. J. Exp. Med. 170:2153-2157.
3. Mall C. et al., 2016. Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogeneic hypersensitivity reactions in a murine model of breast cancer. Oncoimmunology. 5(2):e1075114.
4. Baudino L. et al., 2008. Crucial role of aspartic acid at position 265 in the CH2 domain for murine IgG2a and IgG2b Fc-associated effector functions. J. Immunol. 181(9):6664-9.
5. McDermott D. & Atkins M. 2013. PD-1 as a potential target in cancer therapy. Cancer Med. 2(5): 662–673.
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 (0.2 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
PD-1
Mouse
Sodium phosphate buffer, saccharose
< 5%
0.2 µm filtration
≤ 1 EU/mg (measurement by kinetic chromogenic LAL assay)
In vivo studies, flow cytometry, ELISA
Each lot is functionally tested by flow cytometry.
CONTENTS
Contents
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Product:Anti-mPD-1-mIgG1e3 (4C11)
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Cat code:mpd1c2-mab15-1
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Quantity:1 mg
Shipping & Storage
- Shipping method: Room temperature
- -20 °C
- Avoid repeated freeze-thaw cycles
Storage:
Caution:
Details
Immune checkpoint signal: PD-1 and PD-L1
— PD-1 (programmed cell death 1; also known as CD279) is a type I transmembrane protein expressed at the cell surface of activated and exhausted conventional T cells. PD-1 is an inhibitory immune checkpoint that prevents T-cell overstimulation and host damage. PD-1 interaction with its ligands PD-L1 and PD-L2 induces inhibition of TCR signaling [1].
— PD-L1 (programmed cell death ligand 1; also known as CD274 or B7-H1) is a transmembrane protein expressed at the cell surface of hematopoietic and non-hematopoietic cells and is induced by pro-inflammatory cytokines, such as in the tumor microenvironment [1]. PD-L1 is one ligand for PD-1, an inhibitory immune checkpoint receptor that is expressed by activated and exhausted T cells. PD-1:PD-L1 interaction induces inhibition of TCR signaling, thereby preventing T-cell overstimulation and host damage [1].
PD-L1 expression is an immune evasion mechanism exploited by various malignancies and is generally associated with poorer prognosis [2]. Specifically, over-expressed PD-L1 on tumor cells and tumor-infiltrating immune cells, such as macrophages, can bind to PD-1 on cytotoxic T cells, and ultimately inhibit the anti-tumor T cell response [3, 4]. Thus, due to PD-L1’s instrumental role in immune evasion by cancer cells, there are numerous inhibitors in development as promising immuno-oncology therapies. Notably, Atezolizumab (also known as MPDL3280A), a fully humanized IgG1 (N298A) mAb that blocks the interaction of PD-L1 with PD-1 and induces anti-tumor immune reactivation, has been approved by the FDA for combinational use in the treatment of lung and breast cancer [3, 5].
References
1. Ribas A. and Wolchock J.D., 2018. Cancer immunotherapy using checkpoint blockade. Science. 359:1350-55.
2. Sun, C. et al. 2018. Regulation and Function of the PD-L1 Checkpoint. Immunity 48, 434-452.
3. Kythreotou, A. et al. 2018. PD-L1. J Clin Pathol 71, 189-194.
4. Lau, J. et al. 2017. Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice. Nat Commun 8, 14572.
5. Heimes, A.S. & Schmidt, M. 2019. Atezolizumab for the treatment of triple-negative breast cancer. Expert Opin Investig Drugs 28, 1-5.
DOCUMENTS
Documents
Technical Data Sheet
Validation Data Sheet
Safety Data Sheet
Certificate of analysis
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