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Antibody

Synthetic DNA’s Role in Advancing Next Generation Checkpoint Inhibitors for Cancer Immunotherapy

An innovative and original synthetic DNA platform created by Dr. David Weiner and team at Wistar’s Vaccine & Immunotherapy Center continues to make great strides in cancer immunotherapy.

Monoclonal antibody (mAb) therapy is one of the most successful approaches for cancer treatment, representing a specific method to zero in on a defined molecular target in the tumor. Antibody technology is central for cancer immunotherapy, which relies on the ability of mAbs to take the breaks off our immune system by inhibiting immune checkpoint molecules. Traditional mAbs are created from cell lines in highly sterile manufacturing plants and are difficult and expensive to make. The Weiner Lab has overcome challenges associated with therapeutic antibody production by developing a novel molecular platform that delivers DNA instructions to a patient that allow the patient’s body to become the production site of its own highly personalized mAbs.

DNA-encoded monoclonal antibodies (DMAbs) are the resulting products of DNA-delivered instructions for the body to make monoclonal antibodies using its own protein manufacturing machinery. The Weiner Lab is advancing this novel technology for cancer and infectious disease immunotherapy.

In a study that was recently published in the journal Oncotarget, they created synthetic DNA-encoded checkpoint inhibitor antibodies targeting the PD-1 checkpoint molecule. Preclinical data presented in this study demonstrated that a single injection of the highly optimized DMAb versions of PD-1 checkpoint inhibitors is sufficient to achieve a robust expression that lasts for several months in mice. 

These results reinforce the findings of a previous study, published a few months ago in the journal Cancer Research, in which Weiner and colleagues developed synthetic DNA-encoded checkpoint inhibitor antibodies targeting CTLA-4, another important cancer checkpoint molecule that blocks anti-cancer immunity.  

References: 

Simplifying checkpoint inhibitor delivery through in vivo generation of synthetic DNA-encoded monoclonal antibodies (DMAbs), Perales-Puchalt A. et al., Oncotarget, 2019

Synthetic DNA-encoded monoclonal antibody delivery of anti-CTLA-4 antibodies induces tumor shrinkage in vivo, Duperret E.K. et al., Cancer Research, 2018