CIS Pharma develops novel antibody-drug-conjugates (ADCs) based on our proprietary Cellophil® polymer platform. The Cellophil® polymers serve as a backbone that is loaded with cytotoxic drugs. The backbone together with its cargo is subsequently linked to a target-specific antibody. As a result, Cellophil® ADCs offer increased potency by linking a higher number of cytotoxic drug molecules to the antibody compared to conventional ADCs.

Conventional ADCs use covalent linkers to load cytotoxic drugs onto the antibody directly. This approach limits the number of cytotoxic drugs that are carried to the tumor cells. Nevertheless, antibody-drug-conjugates combine target-specificity of an antibody to a tumor antigen with a potent cytotoxic drug. In comparison to the administration of a cytotoxic drug alone, side effects are significantly reduced as normal cells remain unimpaired during treatment.

CIS Pharma combines biology with our expertise in chemistry and our proprietary polymer technology to create Cellophil® ADCs. The Cellophil® polymers increase the solubility of hydrophobic cytotoxic drugs that suffer from low bioavailability. Our Cellophil® ADCs have a higher drug-to-antibody-ratio (DAR) compared to conventional ADCs. The approach allows different classes of cytotoxic drugs to be linked to the backbone. A variety of target-specific agents such as antibodies, antibody fragments, aptamers and smaller homing agents can be loaded with the Cellophil® cytotoxic drug carrier. Cellophil’s® resistance to degradation may be an advantage over currently used polymers since shelf life in solution and circulation time might be increased. Cellophil® can be designed to be cleared by renal excretion after degradation of the antibody and release of the payload.


Mode of action of Cellophil® ADCs

1 Cellophil® ADC binds to a tumor specific antigen, e.g. an overexpressed cell surface receptor. 2 The Cellophil® ADC/receptor complex is internalized into the cell (membrane). 3 Membrane vesicles are formed around the ADC/receptor complex and the vesicles are transported to specific cell organelles. 4 The membrane vesicles containing the ADC/receptor complex are fused with a lysosome. 5 The low pH and high content of proteolytic enzymes in the lysosome leads to the degradation of the antibody/receptor complex as well as the linkers which bind the cytotoxic drug to the Cellophil® polymeric backbone. 6 The cytotoxic drug is released from the lysosome. 7 The released cytotoxic payload leads to the death of the cancer cell, e.g. by inhibition of DNA replication.

The ERP effect in tumor therapies

The tissue of a solid tumor differs from healthy tissue with respect to the appearance of blood and lymph vessels. This leads to abnormal molecular and fluid transport. A high molecular weight substance (up to 40,000 Da) can easily enter the tumor tissue whereas it does not penetrate healthy tissue. This phenomenon is called the enhanced permeability and retention (ERP) effect and can be used for cancer therapies as high molecular weight substances tend to accumulate in tumor tissue. Cellophil® can be used as a carrier for low molecular weight drugs. This increases their overall molecular weight. Thus, Cellophil® drug carriers accumulate specifically in the tumor tissue and are not able to enter healthy tissue. While cancer cells are effectively killed by the cytotoxic payload, side effects are reduced as the healthy tissue remains unimpaired. The specificity to target cancer cells is further improved by functionalization of the Cellophil® drug carriers with a “homing” agent.