Functionally Masked Antibody to Uncouple Immune-Related Toxicities in Checkpoint Blockade Cancer Therapy.

Of the existing immunotherapy drugs in oncology, monoclonal antibodies targeting the immune checkpoint axis are preferred because of the durable responses observed in selected patients. However, the associated immune-related adverse events (irAEs), causing uncommon fatal events, often require specialized management and medication discontinuation. The study aim was to investigate our hypothesis that masking checkpoint antibodies with tumor microenvironment (TME)-responsive polymer chains can mitigate irAEs and selectively target tumors by limiting systemic exposure to patients. We devised a broadly applicable strategy that functionalizes immune checkpoint-blocking antibodies with a mildly acidic pH-cleavable poly(ethylene glycol) (PEG) shell to prevent inflammatory side effects in normal tissues. Conjugation of pH-sensitive PEG to anti-CD47 antibodies (αCD47) minimized antibody-cell interactions by inhibiting their binding ability and functionality at physiological pH, leading to prevention of αCD47-induced anemia in tumor-bearing mice. When conjugated to anti-CTLA-4 and anti-PD-1 antibodies, double checkpoint blockade-induced colitis was also ameliorated. Notably, removal of the protective shell in response to an acidic TME restored the checkpoint antibody activities, accompanied by effective tumor regression and long-term survival in the mouse model. Our results support a feasible strategy for antibody-based therapies to uncouple toxicity from efficacy and show the translational potential for cancer immunotherapy.

Chitosan-Polypyrrole Fiber for Strain Sensor.

A chitosan/polypyrrole composited fiber as bio-compatible materials for artificial muscles is investigated. The chitosan/polypyrrole fiber (CPF) is fabricated by in-situ chemical polymerization of pyrrole monomer solution using FeCl3 as an oxidant. The electrical resistivity of the fiber is changed according to the strain variation applied to the both ends of the specimen. The sensor built by using the CPF has a higher gauge factor (4) compared to conventional metal strain gauges (~2) indicating a suitable material for delicate force control in sensing work.