ADC Development Services Targeting cKIT

It has been reported that cKIT expression is observed in many cancers, and this molecule is associated with therapeutic and prognostic consequences in patients with small cell lung cancer (SCLC), acute myelogenous leukemia (AML), and gastrointestinal stromal tumors (GIST). In order to facilitate the research of anti-cancer drugs, Creative Biolabs offers high-quality antibody-drug conjugates (ADCs) development services based on our experienced staff, the state-of-the-art facility, quality by design, and traceable batch records for our worldwide customers. We are fully confident that our products and services can speed up your anti-cKIT ADC development process.

Introduction of cKIT

cKIT (CD117), a type III receptor tyrosine kinase (RTK), encodes a tyrosine kinase growth factor receptor for stem cell factor (SCF). The RTK family is categorized into three domains, namely a hydrophobic transmembrane, an extracellular ligand-binding domain, and a cytoplasmic domain with tyrosine kinase activity. Deregulation of cKIT can result in cancer in different ways, such as gain of function, loss of function, overexpression, and point mutations. cKIT is involved in intracellular signaling, and the mutated form of cKIT plays a crucial role in occurrence of some cancers. Besides, the function of cKIT has led to the concept that inhibiting cKIT kinase activity can be a target for cancer therapy. Several evidence reveals that targeting cKIT by ADC is a novel promising approach for cancer treatment.

Fig.1 CD117 is amplified (a) or mutated (b) in a variety of cancers. (Foster, 2018)

Anti-cKIT ADC in SCLC, AML, Gastrointestinal Stromal Tumors (GIST)

Gain-of-function mutations resulting in constitutive cKIT activation play a vital pathogenic role in SCLC, AML, and GIST. Treatment with the small-molecule inhibitors such as imatinib and regorafenib results in resistance (cKIT mutant tumors) or limited activity (cKIT wild-type tumors). Nowadays, emerging results have encouraged researchers’ attempts toward improvement of using cKIT as a capable ADC target for cancer therapy. Taking one anti-cKIT ADC for example, LOP628, it is an ADC composed of the cytotoxic maytansinoid, DM1, covalently linked via N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) to lysine residues of the antibody LMJ729. LOP628 becomes internalized and lysosomally processed to yield the active catabolite Lys-N^ε-MCC-DM1, resulting in cell-cycle arrest and potent activity against mutant and wild-type cKIT-positive tumor models. The compelling activity in models of SCLC, AML, and GIST suggests this anti-cKIT ADC has the potential for treating patients with these three diseases.

What Can We Do for You?

The promising results of anti-cKIT ADCs for treatment of cancers have been observed in different studies. Creative Biolabs now offers one-stop integrated ADC development services for clients all over the world. Our ADC development services include but not limited to the following：

Customized ADC design
Antibody production, screening, optimization and conjugation for ADC development
Customized linker-payload synthesis
Process development and optimization of ADC conjugation
ADC in vitro Analysis
ADC in vivo Analysis
ADC manufacturing

If you are interested in generating an own anti-cKIT ADC, we are more than happy to share our experience with you. Please contact us to obtain a quote or to schedule a teleconference.

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