What Are ADCs?

Targeting antibodies are attached to chemotherapeutic molecules through a linker to create antibody-drug conjugates or ADCs. The fundamental idea behind creating an ADC is to combine the potency of the drug's cytotoxicity with the utmost accuracy with which the antibody directs the drug toward the cell surface. The ADC interacts with the target receptor on the cell surface before being ingested by endocytosis. CD BioGlyco provides Glycosylation Site-specific ADC Development Services and Anti-glycan Antibody Development Services for customers to help study Siglec-targeted ADCs.

Fig.1 Mechanism of action of ADCs. (Scotti, et al., 2015)

What Is Siglec-Targeted ADC

Anti-Siglec antibodies (Abs) can eliminate Siglec-expressing cells by either directly inducing apoptosis or enlisting the aid of immune system effector cells. When ligated by Ab, many Siglecs internalize quickly, which can reduce complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). This characteristic has also been used to create Ab drug/toxin conjugates. With little off-target damage, ADCs use a particular mAb as a vehicle to deliver powerful cytotoxic medicines to tumor cells.

Fig.2 Antibody based molecules targeting Siglecs. (A) mAbs against Siglecs. (B) Targeting Siglecs with chimeric antigen receptors (CARs) and bi-specific Abs. (C) Targeting cancer-associated glycans of tumor cells. (Lenza, et al., 2020)

Potential Applications of Siglec-Targeted ADC in Therapies

Acute lymphoblastic leukemia patients can now use the anti-CD22 ADC therapy inotuzumab ozogamicin, which combines the epratuzumab anti-CD22 mAb with the cytotoxic antitumor antibiotic calicheamicin. In Phase I investigations for hairy cell leukemia, moxetumomab pasudoto, an ADC that combines anti-CD22 with PE38, has also produced positive results. The first FDA-approved ADC against CD33 is gentuzumab ozogamicin, a humanized anti-CD33 mAb covalently bonded furthermore to calicheamicin.

CD BioGlyco has established advanced platforms to provide customized solutions according to our clients’ every special need. if you are interested in our services, please feel free to contact us for more detailed information.

References:

1. Lenza, M.P.; et al. Current status on therapeutic molecules targeting SIGLEC receptors. Cells. 2020, 9(12): 2691.
2. Scotti, C.; et al. Antibody-drug conjugates: Targeted weapons against cancer. Antibody Technology Journal. 2015, 1.