Pulse 76: 3D Molecular Engineering for Cancer Immunotherapy

13 August 2018
Giulio Prisco

3D Molecule Model

A new molecular engineering technology dubbed PSI, developed by scientists at Scripps Research and Bristol-Myers Squibb (see below), acts like an atomic glue gun, and enables building of therapeutic molecules with preprogrammed spatial configurations. This is important because the 3D shape of a molecule can be critical to the therapeutic activity of the molecule.

According to one of the senior researchers, PSI overcomes a significant hurdle to discovering the next generation of innovative medicines. The scientists expect to use PSI to build cyclic dinucleotides (CDNs), drugs that activate the body’s immune system against cancers.

“CDNs show incredible promise for activating the immune system against cancers, but until now there was no simple way to control their stereochemistry,” said another researcher. “The ability to efficiently and inexpensively create pure stereoisomers will provide a powerful tool to advance CDN research.”

Precisely controlling the 3D architecture of cancer immunotherapy drugs. Scientists at Scripps Research and Bristol-Myers Squibb have created a powerful new tool for precisely controlling the 3D architecture (stereochemistry) of some promising new drugs that target genetic molecules and other disease targets. A study published in Science describes a new technique dubbed phosphorus-sulfur incorporation (PSI). The researchers have used PSI to generate pure stereoisomers of cyclic dinucleotides (CDNs), the basis of CDN drug candidates that have generated much excitement as a new type of cancer immunotherapy.

Bioinformatics predicts response to cancer immunotherapy. Scientists at the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy have developed a new way to use bioinformatics and big data analysis to determine how a patient's immune system recognizes tumors and responds to immunotherapy. The new technique, called “Mutation-Associated Neoantigen Functional Expansion of Specific T Cells” (MANAFEST), is described in a paper published in Cancer Immunology Research. The scientists hope to use this procedure to predict responses to immunotherapy in many types of cancers, and develop the best treatment options for cancer patients.

New compounds reverse human cell aging. Researchers at University of Exeter have shown that key aspects of the aging of human cells can be reversed by new compounds. In a laboratory study of endothelial cells, published in Aging, the scientists tested compounds designed to target mitochondria. The number of senescent cells (older cells that have deteriorated and stopped dividing) was reduced by up to 50 percent. According to the researchers, the findings show potential to tweak the mechanisms by which this aging of cells happens, and represent a breakthrough that could be a basis for a new generation of anti-degeneration drugs.

Soluble curcumin can be an effective anti-cancer agent. Bioengineers at UI Engineering have found a way to make the herbal supplement curcumin soluble, enabling delivery to cancer cells. This may permit drugs to leverage known anti-cancer properties of curcumin. A study published in PNAS describes a sophisticated metallocyclic complex using platinum that has not only enabled curcumin's solubility, but whose synergy has proven 100 times more effective in treating various cancer types, such as melanoma and breast cancer, than using curcumin and platinum agents separately.

Toward rapid and effective response to heart attacks. Scientists at NC State University and UNC Chapel Hill have developed a drug-delivery system that allows rapid response to heart attacks without surgical intervention. A study published in ACS Nano reports that, in laboratory and animal testing, the system proved to be effective at dissolving clots, limiting long-term scarring to heart tissue, and preserving more of the heart's normal function.

New imaging tool for living cells. Researchers at Columbia University have shown that a widely used chemical tracer, combined with a cutting-edge microscope, can track metabolic changes within the living cells of animals. A research paper published in Nature Communications describes a new technique that combines a widely used chemical tracer, D2O, or heavy water, with a relatively new laser-imaging method called stimulated Raman scattering (SRS). The technique's potential applications include helping surgeons quickly and precisely remove tumors, and helping physicians detect head injuries and developmental and metabolic disorders.

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