Joseph Glorioso, III: Turning Bad Guys into Good Guys

Year Funded: 2018

Joseph Glorioso, III: Turning Bad Guys into Good Guys

“I was originally trained as a virologist,” says Joseph Glorioso, III, MD, PhD, of the University of Pittsburgh School of Medicine Department of Microbiology and Molecular Genetics (Pittsburgh, Pa.).
Viruses naturally cause disease, generally by growing within specific cell types in the body, which leads to cell destruction and virus spread. Based on the tremendous amount of accumulated knowledge about virus molecular biology and pathology, it has become clear that through virus genetic engineering, viruses can be tamed and directed to kill cancer cells rather than cause disease.

“When viruses began to emerge as potential weapons in the war on cancer, I became very excited about the phenomenal potential of cancer killing oncolytic viruses and I wanted to be a part of bringing this new cancer therapy to patients.”

Dr. Glorioso is, indeed, making it happen. With a grant from the Alliance for Cancer Gene Therapy (ACGT), he is applying what he knows about the biology of herpes simplex virus to design effective new ways to repurpose its power for the discovery and destruction of tumors and stray metastatic cancer cells.

These viruses are designed to function as anti-tumor vaccines that work in the body by extracting tumor-related proteins called antigens rather than through injection of tumor vaccine material into skin or muscle. This strategy depends on the body’s amazing ability to naturally discover the tumor antigens that have been difficult to pin down by studies of tumor proteins. The Holy Grail of this quest is to be able to introduce cancer-fighting viruses that function effectively through a patient’s bloodstream, triggering the patient’s immune system to attack the tumor.

The challenges are many and complex, but one issue Dr. Glorioso is determined to overcome is the problem of a patient’s immunity to previously encountered viruses, such as herpes simplex virus.

“Under normal circumstances, a healthy immune system would consider a virus to be an invading pathogen and through anti-viral antibody production, it would neutralize the virus’ ability to infect cells,” says Dr. Glorioso, “but to fight cancer with viruses, we need the immune system to stand down until we can get those viruses into the tumors.

To keep those viruses alive and active, we need to put them to work in stealth mode. We need to cloak our cancer targeted viruses so they’re not recognized and destroyed by a person’s immune memory before they can infiltrate cancers. Once they do, the resulting tumor cell debris will be recognized as foreign and stimulate the patient’s immune system to join in the assault on the cancer.”

“A huge amount of progress is being made in fighting cancer with cell and gene therapies,” says Dr. Glorioso. “I’m convinced we’re going to solve cancer with immune system solutions — just like we solved smallpox and polio with vaccines. Twenty-five years from now, I’m confident we will have an immune solution for most cancers.”

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