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1. MoA：
(1) CCR8 is a G protein-coupled receptors (GPCRs) that is expressed on Th2 cells, monocytes and NK cells. CCR8 was also expressed in Treg cells, and was highly expressed in tumor-infiltrating Treg cells, and was lower in thymocyte, spleen and peripheral blood. CCR8 participates in the development of various tumors and mediates tumor immunity through the interaction with its ligand. The high specific expression of CCR8 on Treg at tumor indicates that CCR8 is an excellent biomarker of Treg cells for tumor and a potential tumor immune target.
(2) CCR8 and Treg cell-mediated immunosuppression CCR8+regulatory T cells (Treg cells) are the driving factors of immunosuppression. CCR8 is an immunosuppressive receptor that mediates the immune escape of tumor cells. CCL1 can attract FOXp3+CCR8+Treg cells to infiltrate into tumor tissue through the interaction with its ligand CCR8, and present immunosuppressive function. At the same time, CCL1 can induce the up-regulation of CCR8 expression on the surface of FOXp3+Treg cells and induce Ca2+ flow, which cause the up-regulation of stat3 dependent Foxp3, CD39, IL-10 and granzyme B expression, thus enhancing the immunosuppressive activity of these tumor-infiltrating Treg cells; CCR8 was highly expressed on FOXP3+Tregs in tumor tissue of patients, but significantly decreased in blood. This is different from targets such as CCR4, CTLA-4 and CD25. The specific expression of CCR8 on tumor site Treg cells makes the development of CCR8 targeted monoclonal antibody drugs is expected to specifically inhibit the function of tumor site Treg and help cancer treatment.
2. Excellent preclinical results:
(1) FACS test showed that the affinity with hCCR8 and cynoCCR8 was higher than that of the positive drug (Shionogi S-531011), and it did not bind with hCCR4 cells.
(2) The antibody can effectively block the interaction between CCL1/hCCR8, and strong ADCC and ADCP activities were observed in vitro.
(3) The antibody maintained high stability in accelerated test, low pH condition and human plasma.
(4) It showed excellent tumor inhibition effect in vivo in hCCR8 mice.
1. Asset type: CCR8 humanized antibody
2. Indication: Solid tumor
3. Stage:Preclinical
4. Cooperation: sequence authorization or project transfer
5. Research progress:
(1) Ongoing Preclinical research:
The targeted therapy of CCR8 humanized antibody has the potential to treat multiple solid tumors.
Effectively reduce the immunosuppressive effect of Treg cells in tumor microenvironment.
Shown good target affinity and stability in vitro.
Shown good tumor inhibition ability in vivo.
ACROBiosystems offers a wide selection of Matrigengel basement membrane extracts. Different versions – including phenol red-free, high concentration, iPSC culturing, organoid culturing – are all available for your specific needs to support 3D cell culture!
To enable antibody characterization methodsACROBiosystems has developed a series of enzymes.such as ldeS, SpeB, EndoH, and Endo S proteases, toassist with the characterization of antibodies and theirrelated post-translational modifications (PTMs)
ComboX is a new brand of ACROBiosystems. ComboX products include our Streptavidin series products, coated plates, isotype controls for antibody and fusion protein drug research, and general-purpose antibodies.
50+ targets designed for CAR detection, including PE/FITC/biotin labeled proteins. The key reagents for CD19 and BCMA were FDA DMF filed which can support your IND, NDA and BLA process.
ACROBiosystems developed a series of GMP grade cytokines under the GMP grade quality management system. Those products are all suitable for T/NK cell generation, activation, and proliferation in cell therapy research.
GMP grade cytokines, reagents for cell activation, gene edition, DNA/RNA removal, etc. Particularly focus on product design, quality control and solution-based support to link each phase of your cell and gene therapy journey.
Full length multi-pass TPs with stabilized structure and high bioactivity for immunization, antibody screening, cell based assay and CAR detection, including hot CD20, Claudin 18.2， CD133, GPRC5D，CCR8, CCR5, etc.
A series of immune checkpoints including classic co-inhibitory and co-stimulatory receptors. The comprehensive catalog contains 100+ targets with various species and tags, and the high-quality proteins are in good batch-to-batch consistency.
To meet the needs of ADCs development, ACROBiosystems can provide: A variety of high-quality target proteins; MMPs/Cathepsin/uPA for cleavable linker; Anti-payload antibodies & anti-idiotypic antibodies for immunogenicity and PK analysis; SPR/BLI analytical and ADA development service.
Comprehensive collection of Fc receptor proteins, including their common variants, which can help expedite your antibody development.
Comprehensive cytokine targets including interleukins, growth factors, chemokines, TNFs, etc. are expressed by HEK293 to ensure their natural structure. Their high purity is verified by SDS-PAGE/HPLC/SEC-MALS and high bioactivity is verified by ELISA/SPR/BLI.
Aneuro is ACROBiosystems brand focused on neuroscience research, providing high-quality important proteins including therapeutic and diagnostic research proteins, PFFs and recombinant neuro factors, etc. to advance neuroscience research.
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