Biotechnology Advances for Disease Management

Researchers continue to investigate the role of biotechnology in the management of cancer and other diseases. A few notable examples have been identified by Frost & Sullivan.

Gut microbiome and cancer immunotherapies are among the emerging innovation areas in the global healthcare landscape, yet research at the intersection of these spaces has been limited. New studies are revealing that gut microbiome plays an important role in immunotherapy regulation, especially immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (PD-1) and anti-programmed death ligand 1 (PD-L1). However, because certain aggressive cancers, including triple-negative breast cancer (TNBC), are hard to treat with ICI therapies, scientists are exploring oncolytic viral therapy to enhance ICI treatment efficacy.

Researchers at leading academic institutions and pharmaceutical companies continue to investigate the role of biotechnology in the management of cancer and other diseases. A few notable examples follow.

Leeds Institute of Cancer and Pathology (United Kingdom)

 A Leeds research group and colleagues from the Institute of Cancer Research in London are focusing on the use of oncolytic viruses for the management of solid and hematological malignancies. The researchers have demonstrated that a naturally occurring reovirus can pass directly from the blood to the brain through a protective membrane surrounding it to infect cancer cells and stimulate immune response. A small study was conducted on nine patients with fast-growing gliomas or cancer that had spread to the brain from other parts of the body. The patients’ tumors already were scheduled to be surgically removed; the experimental treatment was administered in a single dose through an intravenous drip in the days leading up to surgery. Findings were published in the journal Science Translational Medicine. Based on this success, a new clinical trial is underway involving the combined administration of reovirus and standard radiotherapy and chemotherapy after surgery.

Ottawa Hospital Research Institute (Canada)

The institute is exploring the use of oncolytic viruses and checkpoint inhibitors for cancer management. A recent study funded by the Alliance for Gene Therapy found that combining oncolytic viral and ICI treatments enhanced response in TNBC—the most aggressive form of breast cancer. The study showed a cure rate of 60 to 90 percent in TNBC mouse models after combined oncolytic virus and checkpoint inhibitor treatment, compared with zero percent for the inhibitor alone and between 20 and 30 percent for the virus alone.

University of Chicago Medicine

University scientists have reported that the assemblage  of  gut microbiome  improves  the efficacy of anti-PD-1 therapy in patients with advanced melanoma. Bacterial species including C. aerofaciens, E.  faecium  and B.  longum were  more prevalent  in  the intestines  of patients  who responded  to  ICI therapy in a study of 42 people being treated for metastatic melanoma. Thirty-eight of the subjects received an anti-PD-1 and the others received a related therapy; the 16 who responded to treatment showed a much higher presence of the defined bacterial species, which “appears to enhance T-cell infiltration into the tumor microenvironment and augment T-cell killing of cancer cells, increasing the odds of a vigorous and durable response,” the university reported. The study’s director said it suggests “a causal relationship” between the bacteria and the therapy response.  The researchers’ next steps are to identify additional bacteria that are either potentially beneficial or harmful and the mechanisms by which they influence immune system response.

Shire Pharmaceuticals (Dublin, Ireland)

Shire recently has been focusing on therapies for the management of rare diseases, but is also targeting a common virus. In January, the company received a breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for maribavir (SHP620), an investigational benzimidazole riboside that is being clinically investigated for cytomegalovirus (CMV) treatment in transplant patients who are resistant to or show side effects from other therapies.

In the United States, half of all adults are thought to be infected with CMV, a type of herpes virus, by age 40; the virus has no cure but rarely is a problem—or even noticed—in healthy individuals.  But in those with weakened immune systems, including transplant recipients, CMV infection can be fatal. Maribavir  is  known  to  target  a  key  CMV  enzyme  to inhibit  the  replication  and  encapsidation  of  DNA.  The drug also prevents viral capsid escape from nucleids in infected host cells.  Shire’s Phase 3 study is expected to be completed in May 2019.

The Road Ahead

Priming the cancer immune microenvironment with oncolytic viral therapies could lead to groundbreaking innovations that will alter the course of cancer management in the next decades. The University of Chicago Medicine scientists are among those taking the first steps along this road. In addition, rare disease management is a growing area of interest among global pharma companies and biotech start-ups. Thousands of rare diseases (defined in the United States as one affecting fewer than 200,000 people, and in the European Union as one affecting fewer than 1 in 2,000 people) have been identified; most have no treatment. The FDA’s Office of Orphan Products Development administers grant programs to offset the financial risks of sponsors’ development of biologics or other products that can diagnose or treat rare diseases.  A company could expand a successful treatment’s use to more profitable indications, creating a win-win situation—a trite, yet appropriate characterization—for itself and a larger pool of patients.

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