Protein therapeutics have been enormously successful as witnessed by their dominance in FDA approved medicines. Of these therapeutics, antibodies, and antibody-based drugs such as antibody-drug conjugates (ADC) form a major portion of biologics. ADCs improve the therapeutic efficacy of anti-cancer drugs by concentrating their effects on cancer cells specifically. Protein therapeutics also offer the potential to treat several cellular deficiencies by utilizing proteins as intracellular drugs. However, due to their bulky size and hydrophilicity, their use has been limited to extracellular targets. The current work combines the advantages of both fields, namely antibody-drug conjugates, and protein therapeutics to achieve targeted delivery of proteins using polymer brushes. Protein-antibody conjugates (PACs) were constructed using two bio-orthogonal click chemistries. Furthermore, we show that the protein cargo encapsulated by polymer brushes of PACs prevent the protein from proteolytic digestion, and the PACs exhibit antibody-receptor mediated uptake into receptor positive cancer cells. The therapeutic ability of anti-CD4 antibody conjugated polymer brushes is then demonstrated by selective toxicity in CD4+ mT-ALL cells over CD4- T-cells.

Protein-antibody conjugates (PACs) for targeted intracellular delivery of therapeutic proteins

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.