With years of experience in antibody development and bioconjugation, BOC Sciences provides exceptional ADC design and construction services for AXL Targets. We have successfully developed numerous cytotoxins, such as auristatins, calicheamicins, camptothecins, daunorubicins/doxorubicins, duocarmycins, maytansinoids, piericidins and PBDs. All of our cytotoxins and linkers are characterized by state-of-the-art analytical techniques, including 1H-NMR, MS, HPLC, GC, IR, and TGA.
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AXL belongs to the TAM family of receptor tyrosine kinases, members of which also include Mer and Tyro-3. As a receptor tyrosine kinase (RTK) family, TAM has gradually become one of the research hotspots in recent years. The protein members of theTAM family are mainly composed of extracellular segment, transmembrane segment and intracellular segment. The intracellular segment has kinase activity and can participate in the transmission of various signals in normal cells and tumor cells. As a member of the TAM receptor family, AXL protein is highly expressed in various tumor cells. It was originally found in patients with chronic myeloid leukemia. AXL is widely expressed in monocytes, macrophages, platelets, endothelial cells, cerebellum, heart, skeletal muscle, liver and kidney and other cells and organs. In the study of many cancer cells, it was found that AXL gene was overexpressed or ectopic expression in hematopoietic cells, mesenchymal cells and endothelial cells. Therefore, AXL represents a promising therapeutic target in cancer management.
Fig. 1. AXL activation and functions (International Journal of Biochemistry and Cell Biology. 2021, 139: 106057).
There are three main mechanisms by which AXL receptors promote cell survival. (1) Activated AXL can prevent cell apoptosis, but do not stimulate cell proliferation. (2) AXL can enhance the proliferation of cells, but does not inhibit the process of apoptosis. (3) AXL can simultaneously promote cell survival and proliferation. All three mechanisms suggest that activated AXL receptors favor tumor growth. Studies have shown that the high expression of AXL and its corresponding high activity can enhance the survival and migration of tumor cells, while reducing the expression of AXL or blocking its activity can inhibit the growth and metastasis of these tumor cells. Therefore, for cancer patients with high AXL expression, AXL inhibitors can be a class of drugs with clinical application value for the treatment of cancer.
As a potential target for ADC drug development, AXL has been widely used in targeted immunotherapy for various hematologic and solid tumors. Enapotamab Vedotin is an AXL-targeted ADC drug conjugated to anti-AXL monoclonal antibody and the antimitotic drug MMAE. Preclinical studies show that Enapotamab Vedotin (2 and 4 mg/kg) exhibits antitumor effects in osimertinib-resistant patient-derived xenograft models. Currently, phase I/II studies are underway on the safety of Enapotamab Vedotin in solid tumors.
CAB-AXL-ADC is another clinical stage ADC development drug. In the tumor microenvironment, CAB-AXL-ADC selectively binds to human and cyno AXL expressing cells. In vitro experiments show that CAB-AXL-ADC induces cytotoxicity in AXL-expressing human tumor cells, and in vivo inhibits tumor growth in human tumor xenograft models such as lung, prostate, and pancreas. Currently, a Phase I clinical trial of CAB-AXL-ADC in patients with advanced solid tumors is ongoing, as well as a Phase II trial combining CAB-AXL-ADC with PD-1 inhibitors.
AXL has been shown to be overexpressed in various cancers, such as prostatic cancer, gastric cancer, breast cancer, colorectal cancer, and NSCLC cancer. Studies have indicated that AXL overexpression is associated with resistance to many epidermal growth factor receptor (EGFR)-, signal-regulated kinase (ERK) - or phosphatidylinositol-3-kinase (PI3K)-inhibitory target drugs. For example, in NSCLC, AXL expression is higher in mesenchymal cancer cells than in epithelial cancer cells. BOC Sciences released a complete set of ADC drug development services for various targets to help pharmaceutical partners drive forward the development of innovative cancer treatments. Our AXL-targeted ADC development services including:
BOC Sciences leverages our state-of-the-art technology platform to provide a broad range of ADC development services for solid tumors. Our services include target screening services for various types of cancer, modification of humanized monoclonal antibodies, payload and linker synthetic route design and DAR characterization. Our scientists can quickly and efficiently design and create the best ADC product for your drug discovery program. If you are interested in our ADC-related services for AXL-targets, please click here for more information.
Scientists from BOC Sciences provide a full suite of development services for client's research targets or oncology indications. Our services cover antibody modification, bioconjugation, small molecule synthesis, cGMP manufacturing and multiple analytical characterization support services.