Cambridge Healthtech Institute’s Mary Ruberry spoke with Felix Hart of Glycotope GmbH. Felix Hart will be presenting on “Sweet Delivery of the Bitter – Using Carbohydrate-Targeting Antibodies for Tumor-Specific Delivery of Cytotoxic Drugs” at the 3rd Annual “Antibody-Drug Conjugates” conference taking place January 19-20, 2016, as part of PepTalk in San Diego, CA.

Q1: For your group’s ADCs, what are their specific targets?

We are investigating multiple targets and elucidate their potential to deliver cytotoxic agents into target cells. These targets include a group of antibodies targeting carbohydrate structures or a carbohydrate-peptide mixed epitope which are found on the surface of tumor cells. The combination of peptide sequence and glycan structure of tumor-associated MUC1 (TA-MUC1) is very promising with respect to potency and specificity.

Q2: Were you able to demonstrate tumor specificity?

Tumor specificity is an important safety issue which applies to naked monoclonals but might be even more important for molecules with cytotoxic payloads. In order to avoid or minimize on-target toxicity, specificity of ADC candidates is thoroughly investigated. We confirmed tumor specificity of our antibodies by immunohistochemistry using large panels of healthy and tumor tissues. These are very important studies for safety as well as indication selection to increase the chance of benefits for patients.

Q3: Have your studies shown evidence of intracellular drug delivery?

In the current model for ADC functionality, receptor-mediated internalization results in trafficking into endosomes and lysosomes. Then, the active drug is released by processes which depend on enzymatic reactions or the acidic environment within the lysosome. Using antibody-dye conjugates, we confirmed time-dependent intracellular trafficking into acidic compartments by flow cytometry. Reduced viability in cytotoxicity assays confirmed functional drug delivery.

Q4: Are any of your ADCs in the Clinic?

Within our research and development programs encouraging data was generated which points towards moving into clinical studies.

Q5: What do you see as the future of these molecules?

With recent approvals of ADCs, the field caught much attention. Among all three main components of an ADC, the antibody or target binding scaffold, the linker and the cytotoxic payload, many new approaches evolved. For example, methods for site-specific conjugation and drugs with novel mechanisms of action are being developed to increase homogeneity, safety, and efficacy. Clinical programs will hopefully reveal which conjugation strategy, linker and drugs are best suited to generate safe and potent ADCs.

To learn more about Felix Hart’s presentation at the 3rd Annual “Antibody-Drug Conjugates” conference, visit
CHI-PepTalk.com/Antibody-Drug-Conjugates-Conference