ADC Development Services Targeting LIV1

Antibody-dug conjugates (ADCs) directed toward tumor-specific antigens are clinically proven as effective treatments for both solid and liquid tumors. Studies have shown that LIV1 is a promising candidate for ADC therapy due to its broad expression in a number of cancer indications and limited normal tissue expression. Creative Biolabs offers one-stop development and manufacturing services for your anti-LIV1 ADCs. Whether you require small scale development or commercial scale products, our experts in ADC development and manufacturing can meet your requirements.

Introduction of LIV1

LIV-1 (SLC39A6) is a member of the solute carrier family 39, it is a multi-span transmembrane protein with putative zinc transporter and metalloproteinase activity. The LIV1 subfamily is a highly conserved group of eight transmembrane domain proteins that are mainly situated on the plasma membrane and transport zinc into cells. LIV1 family sequences contain a highly conserved potential metalloprotease motif, which closely resembles the active site motif of matrix metalloproteases and is situated in transmembrane domain V.

Fig.1 Schematic representation of LIV1 secondary structure. (Taylor, 2003)

LIV1 expression has been linked to epidermal-to-mesenchymal transition (EMT) in both normal vertebrate embryo development and preclinical models leading to malignant progression and metastasis. There is evidence of LIV1 interacting with the transcription factors STAT3 and Snail to downregulate expression of E-cadherin to promote EMT. In addition to breast cancer, LIV1 has also been detected in other neoplastic tissue types, such as pancreatic, prostate, melanoma, cervical, and uterine. LIV1 represents a potential point of focus for assessing breast cancer therapy, response to therapy, and risk for metastasis.

Anti-LIV1 ADC in Breast Cancer

LIV1 plays a dual role, functioning in both cell growth via its operation as a zinc transporter, as well as metastasis of breast cancer through its association with matrix metalloproteinases. A novel ADC SGN-LIV1A was designed to target the LIV1 for the treatment of metastatic breast cancer. SGN-LIV1A consists of a humanized antibody conjugated via a cleavable dipeptide linker to monomethyl auristatin E (MMAE). When bound to surface-expressed LIV1 on immortalized cell lines, this ADC is internalized and traffics to the lysosome. SGN-LIV1A displays specific in vitro cytotoxic activity against LIV1-expressing cancer cells. In vitro results are recapitulated in vivo where antitumor activity is demonstrated in tumor models of breast and cancer lineages. These results support the clinical evaluation of SGN-LIV1A as a novel therapeutic agent for patients with LIV1-expressing cancer. What’s more, LIV1 is expressed in all subtypes of breast cancer (including triple-negative breast cancer, TNBC) and SGN-LIV1A is active as a single agent in preclinical models. These data in combination with the recent successes of ADCs support pursuing anti-LIV1 ADC as a new therapeutic modality for refractory metastatic breast cancer and other LIV1-positive indications.

Fig.2 Structure of SGN-LIV1A. (Trail, 2018)

What Can We Do for You?

Creative Biolabs has a series of humanized anti-LIV1 antibodies that bind specifically to the extracellular domain of LIV1, internalize after antigen binding, and traffic to the lysosome. Using these mAbs, we further design and generate many anti-LIV1 ADCs that leverage the specificity of the antibody and the activity of different drug module such as DNA toxin, microtubule toxin and protein toxin to produce a LIV1-directed cytotoxic agent. These ADC products show in vitro and in vivo potency and specificity when treating LIV1-expressing cell lines and tumors.

We have the right experience and expertise as well as perfect technology platform to support your ADC project:

• ADC Antibody Screening
• Antibody Design and Conjugation
• DrugLnk™ Custom Synthesis
• ADC in vitro Analysis
• ADC in vivo Analysis

Creative Biolabs takes full advantage of the best characteristics of mAbs and the potency of cytotoxic molecules to support our easy access ADC programs. If you are interested in our anti-LIV1 ADC development services or our existing products, please feel free to contact us for more information or a detailed quote.

Reference

1. Taylor, K. M.; et al. Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. Biochemical Journal. 2003, 375(1):c

For Research Use Only. NOT FOR CLINICAL USE.