Clinical trials underway Cancer vaccines


By blythe bernhard

St. Louis Post-Dispatch

ST. LOUIS

Is the best treatment for cancer already inside of us?

Research is underway at Washington University to test a new approach to cancer treatment. Beyond traditional therapies like surgery, chemotherapy and radiation, scientists want to know if the human body’s own immune system can attack tumors.

They’re testing personalized vaccines designed to target deadly cancer cells in each patient. A vaccine is any substance that prevents or treats a disease with properties of the disease itself. Scientists know that fighting fire with fire works for many viruses like flu, measles or polio. Now they want to test that theory with cancer, but since every tumor is different, every vaccine will be different.

Advancements in genetic sequencing, or decoding the DNA of cells, have made it easier to figure out what makes tumors unique. Scientists have found potential targets in tumor cells that could cause them to break down. Now they’re passing that knowledge on to doctors to try out in their patients with the most challenging cancers. Clinical trials are now enrolling patients with melanoma, brain cancer and breast cancer.

The concept is hypothetical. The research is experimental. There is no proof that it works.

But after staring down deadly cancers, tumors that have spread, and patients who are out of options, doctors are intrigued.

For decades, scientists have gone back and forth on whether the immune system - the body’s defense mechanism - has anything to do with cancer. In the 1950s a concept called cancer immuno-surveillance took hold, meaning that the immune system could recognize tumor cells as foreign. By the 1970s the theory was rejected after laboratory mice with weak immune systems did no worse than normal mice when they developed cancer.

Most cancer scientists moved on to trying different pharmaceutical routes for new treatments. Robert Schreiber of Washington University wanted to know more about those mice. He started more sophisticated tests with mice that lacked a critical gene that allowed the immune system to make lymphocytes - white blood cells that defend the body against disease.

“What we showed conclusively was mice that had defects in the immune system got tumors more quickly and in higher incidences than normal mice,” Schreiber said.

And with that, the concept of cancer immunology was back.

Cancer Vaccines

The Center for Human Immunology and Immunotherapy Programs at Washington University launched last year with Schreiber as director to help doctors use the immune system to fight cancer and other diseases.

Other medical centers around the world have taken different approaches to cancer immunology. Duke University is working with a polio virus vaccine to induce the immune system to fight brain tumors. The Mayo Clinic is doing a similar trial with a measles vaccine. Other clinical trials involve reprogramming the immune system’s checkpoints that prevent it from attacking certain cells.

Washington University leads the study of personalized cancer vaccines. With help from their genetic sequencing labs, local scientists try to isolate the best antigen targets - or the most dangerous mutated cells - from each patient’s tumor to vaccinate against.

Vaccines are typically viewed as preventive, such as flu shots to help avoid flu infection. Cancers known to be caused by viruses can also be prevented this way. The HPV (human papillomavirus) vaccine can prevent some cervical cancers and the hepatitis B shot protects against development of liver cancer caused by that virus.

Scientists now think vaccines can also be used to stimulate the immune system to fight cancers that are already formed. But without a known virus or other cause, scientists must figure out what differentiates a patient’s tumor cells from healthy cells. Then they must try to vaccinate against mutations, called neo-antigens, that occur only in the bad cells.

The immune system is a finely tuned machine that is difficult to manipulate. One challenge is turning up a patient’s immunity without harming healthy cells, the process that happens in autoimmune disorders like multiple sclerosis. One type of immunotherapy, called checkpoint blockade, is risky because it can backfire and make the patient vulnerable to an overly aggressive or weakened immune response. Cancer vaccines, in theory, could be safer because they activate more highly precise targets.

“The real essence of that vaccine design is picking out the peptides (proteins) that have the strongest interaction with the patient’s immune system,” said Elaine Mardis, director of technology development at the university’s McDonnell Genome Institute. “It’s a different answer for every patient.”

Melanoma

The first human trial to apply this concept included three patients with melanoma whose cancer had spread to their lymph nodes. After surgeries to remove their tumors, their cancerous and healthy cells were sequenced to identify mutations. The patients received an infusion using cells from their own immune systems. The treatments stimulated the immune system through a boost of protective T-cells.

After 20 years of specializing in treating deadly skin cancers, the results published earlier this year were gratifying for Dr. Gerald Linette, a co-leader of the trial. But he urges patience to those looking for quick answers.

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