CINCINNATI -- A new study may show the key to surviving cancer relies heavily on boosting the body’s own immune response system.
Researchers from the University of Cincinnati Cancer Institute are conducting a clinical trial for stage 4, non-small cell lung cancer patients using a combination of immunotherapy drugs. The study will measure reduction of tumors along with long-term survival rate. Iowa-based pharmaceutical company and drug manufacturer NewLink Genetic Corporation sponsors the study.
Researchers have long struggled to boost the immune response system against tumors, according to Dr. John Morris, study investigator, University of Cincinnati professor of medicine and director of the Head & Neck Cancer and Thoracic Cancer program. He said some drugs have shown promise during the last several years, but results tend to vary in individuals. He said they’re recognizing the answer may not lie in a single drug.
“In the last three to five years we’ve had really a surge of new immunotherapies that have really shown effectiveness," he said. “Are there any better? Absolutely, and that’s what trials like this are trying to do is look for even better ways by combinations, by adding new drugs to them.”
The agents being used in the study are drugs tergenpumatucel-L immunotherapy and indoximod with the approved drug therapy docetaxel. He said the drug indoximod helps the body correct its response to cancerous tumors. He said some cancerous tumors secrete an enzyme similar to that of pregnant women that allow foreign genetics to be in the body. He said under normal circumstances, the body would attack a fetus because it would see the father’s genetic material as an invader.
“It turns out many cancers use this system to protect themselves from the immune system,” he said. “So they express high levels of IBO enzyme we call it for short, and indoximod blocks the activity of pathway. And what that does is increase the immune response.”
Once tumors can be identified as an invader, he said they follow up using a lung cancer vaccine created with three genetically engineered types of lung cancer lines. He said the engineered cells attach to cancerous cells, producing an abnormal pattern of protein and sugars, which the body rejects.
“So the idea is to take human lung cancer cells and make them very immunogenic and then you vaccinate the lung cancer patient with them and you get an immune response,” he said. “And some of the early trials really showed that the patients that did get immune responses had a longer survival than those who didn’t. And the idea of adding the indoximod is that you can boost that to a higher level.”
Even if a drug shows amazing results, standard Food and Drug Administration approval takes about 10 years, Morris said. In certain cases, he said they bring the drug to market using accelerated approval while it’s still undergoing testing by the manufacturer. However, if the drug shows evidence not supporting its effectiveness, Morris said the FDA can pull it. He said several years ago a popular breast cancer drug was pulled after discovering unacceptable side effects.
“After the drug was on the market for breast cancer they withdrew the approval, which created lot of anger in women being treated for breast cancer feeling the drug was benefiting them,” he said.
Trials like these are not only crucial for identifying potentially life-saving drugs, but may be a person’s last treatment option, Morris said, as participants are only eligible if they can no longer be treated using conventional therapies. He said it’s difficult to measure the ultimate to earlier stage cancers as participants' immune systems are severely compromised due to advanced stages of their illness. But he said even in those with stage 4 lung cancer, he saw vast improvement using solely the cancer vaccine in a previous study conducted by the National Cancer Institute.
“What was noticed was that patients who developed a strong immune response had a much longer survival -- and these were very, very sick, very advanced patients,” he said. “So in my own practice which is primarily lung cancer, I often encourage patients after the standard best first- or second-line treatment has not worked to really consider a clinical trial.”
In addition to lung cancer clinical trials, NewLink Genetic Corporation sponsored studies using indoximod to treat breast cancer, pancreatic cancer and malignant melanoma. The drug manufacturer is conducting trials in a number of cities using their drug therapies.
"Indoximod, an investigational-use only compound, is being evaluated to determine if it can improve the effectiveness of existing treatments for cancer, including chemotherapeutic and immuno-oncology agents,” said Nicholas Vahania, president and chief medical officer, NewLink Genetics Corporation. "Indoximod studies are in various stages of clinical development and we look forward to seeing the results from our studies and the potential benefits for patients with cancer."
The study conducted by the University of Cincinnati began September 2016 and will continue until 300 patients have been evaluated. Those interested in participating can call the UC Cancer Institute at (513) 584-7698 or email kastla@uc.edu
