New Drug Delivery System via Engineering Bispecific Antibody for Improved Delivery and Efficacy

January 26th, 2023

For over a century, it has been a constant quest in therapeutics to create an efficient drug delivery system to make claims of precision therapy being truly precise. Now, the Institute of Engineering in Medicine (IEM) member Jan. E Schnitzer, CEO & President of the Proteogenomics Research Institute for Systems Medicine (PRISM), has recently published a paper on a new drug delivery system allowing for ultra-low dose therapeutic efficacy. The system involves the first ever engineered “dual precision” bispecific antibody with precise binding to promote delivery and precise blocking to block TGF-β effector function in lung tissue.

The team of researchers involved included members from PRISM, IEM, and the Department of Medicine at the UC San Diego School of Medicine.

Many antibodies and drugs that are designed for precision targeting in diseased organs actually do so below theoretical expectations, and this is due to faulty access to in-vivo precision-targeted therapies. “Drug delivery is at the root of precision medicine diagnostic and therapeutic success and we have a new paradigm with concrete benefits now beginning to be exposed and quantified in our new paper,” says Schnitzer. “Our proteomic/bioinformatics/AI approach to mapping endothelial and epithelial cell barriers in the body for finding useful delivery targets entails multi-modality imaging ranging from EM to our in-house whole body SPECt/CT and intravital microscopy, all integrated with advanced antibody engineering and screening to preclinical animal therapy studies.”

What sets this engineered bispecific quad antibody apart from other therapeutics is that it advances beyond passive transvascular transport, a process that all drugs depend on for targeting inside the tissue. The antibody is able to move into solid tissue, specifically the lungs, using a caveolae-mediated transcytotic mechanism in endothelium in-vivo with 3000x more efficiency in dosage delivery. “This just tells us how big of a barrier the endothelium is to us in preventing the full potency of the drug,” states Schnitzer. “I am always appalled by the high number of drugs we have to give to people. Then we have to go to a doctor for the side effects, and these side effects prevent the benefits of treatment. We cannot solve one problem by creating another one.”

At a basic science level, the therapeutic creates an ideal system for understanding how TGF functions in the body, showing promise for methods such as molecular dissection to strike at molecules minutes after IVF. In a clinical perspective, the therapeutic will be extremely useful for theranostic use, such as in creating an agent that can be used to image, detect and help treat diseases.

PRISM projects to continue to test this approach in cancer and heart clinical trials in 2024. The antibodies targeting tumor caveolae will also be in clinical trials in 2024. “We have an amazing group of chemists working in drug linkage and nanocarriers. We are expanding [our] efforts and look to do so collaboratively with the many IEM faculty who overlap scientifically,” says Schnitzer. “NCI is already making GMP antibodies and paying for the clinical trials, and we currently have a project grant as well. It’s nice to be in the San Diego environment where so many things are going on, and it’s one of the best environments in the world.”

PRISM is a non-profit research institute dedicated to enlightened research and clinical translation to cure human diseases.

To learn more about their work, visit their website here.