Abstract
Checkpoint inhibitors (CPI) have revolutionized the treatment of many solid tumors. However, difficulties in production, stability, the requirement of frequent high doses for antibody administration and long intravenous administration are recurring issues. Synthetically designed DNA-encoded monoclonal antibodies (DMAbs) are a novel delivery method for antibody therapy which could potentially address many of these issues, simplifying design and implementation of MAb-based therapies. DMAbs delivered through plasmid DNA injection and electroporation have been used in preclinical models for the treatment or prophylaxis of infectious diseases, cancer and cardiovascular disease. Our group has recently reported that immune checkpoint blockers can be optimized and delivered in vivo advancing further DMAb technology by optimization, expression and in vivo functional characterization of anti-CTLA4 antibodies. Here we report optimization, expression and binding of DMAbs based on anti-PD1 CPI and discuss the potential of DMAbs in checkpoint immunotherapy.
Highlights
Checkpoint inhibitors (CPI) have revolutionized the treatment of many solid tumors
DNA-encoded monoclonal antibodies (DMAbs) delivered through plasmid DNA injection and electroporation have been used in preclinical models for the treatment or prophylaxis of infectious diseases, cancer and cardiovascular disease
As a follow-up transition study, synthetic DNA sequences were developed to launch DMAb versions engineered as antibody replicas of human anti-CTLA4 therapeutics for either ipilimumab [10] or tremelimumab [11]
Summary
Checkpoint inhibitors (CPI) have revolutionized the treatment of many solid tumors. These therapies have generated an increase in the percentage of cancer longterm survivors by ‘releasing the brakes’ of the immune system to potentiate its antitumor effect in those patients who respond [1]. Our group has recently reported that immune checkpoint blockers can be optimized and delivered in vivo advancing further DMAb technology by optimization, expression and in vivo functional characterization of anti-CTLA4 antibodies.
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