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Can you tell us about your background?
Pinku Mukherjee has spent her life searching for explanations of how the human body works. She had an early interest in biology.
As a child in Bombay, India, she didn’t cry when she scraped her knee. She watched in awe as red blood cells formed “little blobs” that she later learned were clots. When she asked her mother about it, she was told, “That’s what happens. It just clots.”
But Pinku wanted to know more.
An only child, she took after her father, who loved teaching chemistry. He gave up that career for more lucrative work as a Bollywood film producer, but encouraged his daughter to follow her passion for science.
What did you study?
Pinku received a bachelor’s degree in microbiology/ biochemistry from Bombay University and master’s and doctoral degrees from the University of London.
After holding faculty appointments at Pennsylvania State University and Indiana University Medical Center, she worked at the Mayo Clinic in Scottsdale, Arizona, for a decade starting in 1998, where she began extensive work on pancreatic cancer.
What did you do at Mayo Clinic?
At the Mayo, she had worked with Sandra Gendler, a respected tumor biologist. Together they did experiments on mice to see if vaccines could prevent breast and pancreatic cancer. As part of that, Mukherjee began helping Gendler try to determine the role of a protein called MUC1 (muck-one) in the development of cancer.
MUC1 is a protein that’s present on the cells that line most organs. It lubricates and protects them.
But it also has a dark side. When cells become malignant, the MUC1 protein changes and signals tumor cells to multiply.
In their experiments, Gendler and Mukherjee tried to immunize mice against the abnormal MUC1 proteins, just like humans can be immunized against the flu. They injected the mice with vaccines, and as expected, their immune systems revved up for a fight. But instead of succumbing, the tumors continued to grow.
“Something in the tumors was not allowing the immune cells to go in and kill,” Mukherjee concluded.
As an immunologist, her goal became clear: To find a way to block that signal – and allow the immune cells to kill.
What did you do next?
She came to UNCC in 2008 as the Irwin Belk Endowed Professor of Cancer Research. Inaddition to running her lab, Mukherjee teaches immunology and carcinogenesis courses in the biological scienes department and oversees a number of graduate students.
“It’s the best,” she said of the classroom time. “Some of their questions are so out-of-the-box; it’s so much fun to see their point of view. I learn a lot from them.”
At UNCC, she came up with an idea. What about using an antibody?
Mukherjee knew the right antibody could lead straight to her target. Just like every lock has a single key, every antibody is unique and defends the body against a specific foreign body. If she could get to the right target, she might be able to figure out how to kill the tumor cells with their abnormal MUC1 proteins.
She didn’t have such an antibody. But that didn’t stop her.
“Heck,” she said, “let’s make our own.”
A simple experiment
To her, the plan was simple. She would use her mice and their own immune systems to create antibodies.
It’s the same thinking behind the emerging field of immunotherapy which has led to new “targeted” drugs that are giving unexpected years of survival to many cancer patients. Enthusiasm for this groundbreaking therapy is reflected in prime time TV ads that tout the benefits of Opdivo, a new drug that “works with your immune system” to treat lung cancer.
Researchers describe these new therapies as “smart bombs” that go directly to cancer cells, killing them without bothering surrounding healthy cells. That compares with traditional chemotherapy that kills whatever it touches, including healthy tissue.
Mukherjee wasn’t trying to make a drug. (At least not yet.) But, like the smart bombs, she was trying to target the tumor.
Her associates did much of the lab work. It was slow and deliberate. They took cells from tumors in sick mice and injected them into healthy mice. Then they watched. As cancer attacked the formerly healthy mice, their immune systems spewed antibodies to fight off the tumors.
The associates harvested these antibodies and grew even more in petri dishes. Once they identified the most effective antibody, they tested it again and again. They wanted to see if it could be relied upon to target the cancer cells every time, while leaving the surrounding healthy cells alone.
Then, one day in 2009, they called Mukherjee: You’ve got to come and see this.
She hurried down the hall, opened the locked double doors to the lab with her key card, and stepped up to the microscope. She saw what she had been hoping for.
Tumor cells were lit up in fluorescent green, signifying the antibody was binding to the abnormal MUC1 proteins – and ignoring the healthy cells.
Her antibody was hitting its target. Every time.
The next step was to test it on human blood.
For this part of the research, Mukherjee and her associates used samples from both healthy patients and cancer patients that were stored in the lab freezer.
They added the human blood samples to the new antibody. And again they watched for the reaction.
Sure enough, it consistently distinguished between malignant and healthy cells.
When Mukherjee saw the data, she thought: “Oh my gosh. This looks crazy good.”
That Friday night in October 2009, she and her husband poured glasses of red wine as they talked about their day. She got his attention when she told him her lab had tested 200 human blood samples and the antibody had shown nearly 100 percent accuracy.
Puri, an engineer good at analyzing data, remembers his reaction when he saw the numbers: Wow!
He stayed up all night, reading blogs and websites. The more he read about the need for diagnostic tests and cancer treatments, the more excited he got. At 5 a.m., he could no longer wait.
He woke her up and said: You have to start a company.
Coming to market?
Mukherjee and Puri couldn’t stop talking about how they might apply her discovery to the real world.
Maybe the antibody could be used in cancer treatment, to help deliver one of those “smart bomb” drugs to destroy tumors.
Or maybe it could help with diagnosis, by showing which cells are benign and which are malignant. That might help detect cancer sooner, when it’s easier to treat. Or it might help rule out cancer, allowing patients to avoid unnecessary testing or treatments.
But scientific discoveries don’t automatically translate into marketable products. That can take years and lots of money. And many ventures fail.
Puri and Mukherjee didn’t have experience starting a biotechnology company, but they knew they needed to protect her discovery and control how it was used.
By 2011, with help from UNCC, Mukherjee got a patent on her antibody and created a company, now called OncoTab.