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Archive - Sep 30, 2018

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New Cancer Vaccine Shows Early Promise for Patients with HER2-Positive Cancers

Treatment with a HER2-targeted therapeutic cancer vaccine provided clinical benefit to several patients with metastatic HER2-positive cancers who had not previously been treated with a HER2-targeted therapeutic, according to data from a phase I clinical trial presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held September 30-October 3, 2018, in New York City. Among 11 evaluable patients who had received more than the lowest dose of the vaccine, six (54 percent) had clinical benefit. One patient with ovarian cancer had a complete response that lasted 89 weeks, one patient with gastroesophageal cancer had a partial response that lasted 16 weeks, and four patients (two with colon cancer, one with prostate cancer, and one with ovarian cancer) had stable disease. "Immunotherapy marshals the exquisite specificity of the immune system to destroy cancer, and some types may have potentially fewer side effects than traditional chemotherapy," said Jay A. Berzofsky, MD, PhD, Chief of the Vaccine Branch at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. "We are using a vaccine approach to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers. "Our results suggest that we have a very promising vaccine for HER2-overexpressing cancers," continued Dr. Berzofsky. "We hope that one day the vaccine will provide a new treatment option for patients with these cancers."

Bacterial Therapy Tolerable, Shows Early Promise in Patients with Advanced Solid Tumors

A phase I clinical trial investigating the use of bacterial Clostridium novyi-NT spores as an injectable monotherapy had manageable toxicities and showed early clinical efficacy in patients with treatment-refractory solid tumor malignancies, according to data presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held September 30-October 3, 2018, in New York City. "Even after a single injection of this bacterial therapy, we see biological and, in some patients, clinically meaningful activity," said Filip Janku, MD, PhD, Associate Professor at the Department of Investigational Cancer Therapeutics (Phase I Clinical Trial Program), The University of Texas MD Anderson Cancer Center, Houston. "This strategy is feasible, has manageable adverse effects, and could be clinically meaningful in patients with few therapeutic options." While prior anticancer therapies have utilized bacteria, these treatments can cause infection and severe side effects, explained Dr. Janku. C. novyi-NT is an attenuated bacterium that requires a hypoxic environment, a feature of cancerous lesions, to survive and proliferate and therefore does not affect healthy cells, he noted. "By exploiting the inherent differences between healthy and cancerous tissue, C. novyi-NT represents a very precise anticancer therapeutic that can specifically attack a patient's cancer," Dr. Janku said.

Hsp90 Can Stimulate Exosome Release

Researchers from the Verstreken lab (VIB-KU Leuven) in Belgium have identified a completely novel function for Hsp90, one of the most common and most studied proteins in our body. In addition to its well-known role as a protein chaperone, Hsp90 stimulates exosome release. These findings shed new light on treatment strategies for both cancer and neurodegenerative diseases. Hsp90 (heat-shock protein 90), is one of the most abundant proteins, making up one or two out of every hundred proteins in our cells. Heat shock proteins are conserved across animals, plants, and even fungi. Their name dates back to the ‘80, when they were first described as a group of proteins upregulated upon sudden heat stress. The article was published in the September 6, 2018 in Molecular Cell. The article is titled “Hsp90 Mediates Membrane Deformation and Exosome Release." Over the past decades we have learned a significant amount about Hsp90’s function. As a protein chaperone, it assists in the proper folding of other proteins and stabilizes them in case of cellular stress. Hsp90 also helps degrade damaged or misfolded proteins that are beyond salvation. These myriad functions make Hsp90 a crucial governor of protein homeostasis in the cell. New research by Professor Patrik Verstreken and his team at VIB and KU Leuven shows that—independently of its chaperone function—Hsp90 also aids in the release of exosomes. Exosomes are vesicles that are released from the cell after the fusion of vesicle-containing bodies with the cellular membrane. They can contain signaling molecules, but also potentially toxic proteins. “Our experiments in the lab using fruit flies show that Hsp90 can bind and deform cellular membranes,” explains Yu-Chun Wang, one of the researchers in Verstreken’s team.