ADC Development Services Targeting PTK7

Disease relapse after treatment is common in non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and ovarian cancer (OVCA). Preclinical data has demonstrated the potential of the protein tyrosine kinase 7 (PTK7)-targeted ADC to improve the long-term survival of patients with NSCLC, TNBC, OVCA. Empowered by our advanced technical platforms, Creative Biolabs is committed to providing our clients with specialized consultation, one-stop ADC development services targeting PTK7 to our global clients.

Introduction of PTK7 Receptor

PTK7, a single-pass transmembrane receptor with seven immunoglobulin-like domains in the extracellular region and a tyrosine kinaselike domain in the intracellular region, plays an important role in the Wnt signaling pathway. PTK7 undergoes sequential cleavage by ADAM metallopeptidase domain 17 (ADAM17) and γ-secretase, which leads to shedding of the extracellular region of PTK7 (PTK7-ECD) as well as release and nuclear translocation of the intracellular region of PTK7 (PTK7-ICD). PTK7 is a highly conserved member of the pseudokinase family of receptor tyrosine kinases. PTK7 has been reported to have functions in cell adhesion, migration, polarity, proliferation, actin cytoskeleton reorganization, and apoptosis. Currently, PTK-targeted ADCs have been widely studied in the field of cancer treatment due to its nearly fully understood biological characteristics.

PTK7 in WNT and vascular endothelial growth factor (VEGF) signaling. Fig.1 PTK7 in WNT and vascular endothelial growth factor (VEGF) signaling. (Katoh, 2017)

Anti-PTK7 ADC in NSCLC, Breast Cancer, Ovarian Cancer

Previous studies indicated that increased expression of PTK7 found in NSCLC, OVCA, and TNBC. PTK7 signaling could be inhibited by a dominant-negative PTK7 mutant, siRNA knockdown of PTK7 and an antibody against the extracellular domain of PTK7, which resulted in decreased motility and invasivity of cancer cells. Therefore, PTK7 is considered to be a novel prognostic marker for patients with NSCLC, OVCA, TNBC and has potential therapeutic significance. Scientists hypothesized that an ADC based on anti-PTK7 monoclonal antibody (mAb) is able to deliver anti-cancer drugs preferentially into cancer stem cells (CSCs), because PTK7 was upregulated in tumor-initiating cells (TICs) of patient-derived xenograft (PDX) models for NSCLC, OVCA as well as TNBC. PF-06647020, an ADC with an average drug/antibody ratio (DAR) of 4, comprised of a humanized anti-PTK7 mAb, a cleavable valine-citrulline linker and an auristatin, is being investigated in Phase I clinical trial in patients with advanced solid tumors including NSCLC, OVCA and TNBC. The PTK7-targeted ADC finally showed encouraging clinical responses according to the report. Moreover. PTK7-ADC can induce direct and indirect anti-tumor effects through elimination of CSCs and inhibition of tumor angiogenesis, respectively.

Structure of the PTK7-targeted ADC. Fig.2 Structure of the PTK7-targeted ADC. (Damelin, 2017)

What Can We Do for You?

With Ph.D. level scientist team and extensive experience in antibody engineering, synthetic chemistry, and bio-conjugation, Creative Biolabs is dedicated to providing customized ADC development services targeting PTK7 for our honor clients. Creative Biolabs possesses unique ADC Antibody Screening platform to screen "internalizing" antibodies which is crucial in ADC assembly. Our innovative Antibody Design and Conjugation platform and perfect DrugLnk™ Custom Synthesis platform supply diverse design and conjugation strategies as well as custom synthesis of toxins module, linker module and drug-linker complexes. Once the ADC prepared, its biochemical characteristics such as purity, stability, DAR value and the pre-clinical pharmacological parameters can be further assayed in our mature ADC in vitro Analysis and ADC in vivo Analysis platform. Please refer to our technical platforms and contact us for more details.

PTK7-targeted ADC. Fig.3. PTK7-targeted ADC. (Katoh, 2017)

References

  1. Katoh, M. Antibody-drug conjugate targeting protein tyrosine kinase 7, a receptor tyrosine kinase-like molecule involved in WNT and vascular endothelial growth factor signaling: effects on cancer stem cells, tumor microenvironment and whole-body homeostasis. Annals of translational medicine. 2017, 5(23).
  2. Damelin, M.; et al. A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Science translational medicine. 2017, 9(372): eaag2611.

For lab research use only, not for any in vivo human use.


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