ADC Development Services Targeting C4.4A

Overexpression of C4.4A has been shown to correlate with a malignant phenotype and poor prognosis in non-small cell lung cancer (NSCLC). Targeting C4.4A with a specific antibody-drug conjugate (ADC) represents a unique opportunity to selectively treat C4.4A-positive tumors with high unmet medical need. Scientists at Creative Biolabs are highly experienced in full chemical synthesis, chemical modification, as well as bio-conjugation. We are dedicated to helping our clients make progress in ADC development and manufacturing.

Introduction of C4.4A

C4.4A, also known as LYPD3, is a glycosylphosphatidylinositol (GPI)-anchored, highly glycosylated internalizing cell surface protein that has been shown to be upregulated in migrating keratinocytes during wound healing. C4.4A is associated with carcinogenesis in several different cancers such as colorectal cancer, breast and lung cancer. In cancers, C4.4A has been suggested to be involved specifically, in tumor cell invasion via interaction with the extracellular matrix. With the exception of skin keratinocytes and esophageal endothelial cells, C4.4A is strongly overexpressed in NSCLC with preferential expression in squamous cell carcinoma (SCC) subtype. Besides, C4.4A expression is scarce in normal tissues, presenting an opportunity to selectively treat cancers with a C4.4A-directed therapy, such monoclonal antibody and ADC.

Fig.1 Cartoon of the structure of C4.4A. (Jacobsen, 2014)

Anti-C4.4A ADC in NSCLC

BAY 1129980, an anti-C4.4A-ADC, is composed of a fully human C4.4A-targeting immunoglobulin G1 (IgG1) conjugated via cysteine side chains and a non-cleavable alkyl hydrazide linker to a novel, highly potent microtubule-disrupting auristatin W derivative. The C4.4A-ADC is efficacious both in vitro and in vivo in a variety of cancer cell line and NSCLC patient-derived xenograft (PDX) models. Moreover, C4.4A-ADC, in monotherapy or in combination with the current cancer therapies including immune checkpoint inhibitors, could provide new options for treating C4.4A-positive human malignancies with high unmet medical need.

Fig.2 Structure of BAY 1129980. (Willuda, 2017)

What Can We Do for You?

Creative Biolabs caters to the progress of the times and follows the trend of ADC development to offer our clients diverse customized services for ADC design and production. We have put a lot of effort into every aspect of ADC development and achieved good results. Based on our ADC Antibody Screening platform, we are able to generate C4.4A-specific antibodies to be highly selective and rapidly internalized by the cancer cells a. By using our Linker Module, Drug Module and “DrugLnk™ Custom Synthesis” platform, we can select or design the most appropriate linker-payload complex for your ADC, which will have high stability to prevent nonspecific release before reaching the target, and effective release in target tissue to maintain drug efficacy. Furthermore, ADC in vivo Analysis and ADC in vitro Analysis services are also available for our clients to fully charaterize their ADC. If you are looking for ADC development services against C4.4A, Creative Biolabs will be your best choice. Please contact us for more information.

References

1. Jacobsen, B.; et al. C4. 4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma. World journal of clinical oncology. 2014, 5(4): 621.
2. Willuda, J.; et al. Preclinical Antitumor Efficacy of BAY 1129980-a Novel Auristatin-Based Anti-C4. 4A (LYPD3) Antibody-Drug Conjugate for the Treatment of Non-Small Cell Lung Cancer. Molecular cancer therapeutics. 2017, 16(5): 893-904.

For Research Use Only. NOT FOR CLINICAL USE.