Experimental treatment uses modified stem cells to fight cancer

A clinical trial run by UCLA is testing a potentially pioneering form of immunotherapy that could turn a patient’s own body into a powerful weapon against cancer.

Researchers at the university’s Jonsson Comprehensive Cancer Center are reinforcing the immune system’s foundation by genetically modifying bone marrow stem cells, the cellular factories that power immune responses. By arming those cells with receptors that recognize cancer, researchers hope a patient’s body will cure itself from the inside out.

Dr. Antoni Ribas, who is leading the trial, started working on cancer immunotherapy — treatments that alter a patient’s immune response to fend off cancer — more than 20 years ago. He played a key role in the clinical development of Keytruda, Merck’s popular immunotherapy drug used to treat several types of cancer including some types of melanoma (a type of skin cancer), Hodgkin’s disease, some head and neck cancers, some non-small cell lung cancers, and some colorectal cancers. Now he’s turning his attention to another therapy he finds especially exciting.

The immune system defends the body against sickness. T-cells play an integral role. They’re a type of white blood cell that seeks out and destroys diseased cells. The trouble is, T-cells don’t recognize cancerous cells as an adversary, leaving the body vulnerable.

Researchers already know how to get around that by extracting T-cells and adding the genetic code for receptors that detect cancer. The problem? Eventually those super-powered T-cells stop working. “We realized the immune system cells that we give back have a limited life span,” Ribas said.

That’s where the UCLA trial comes in.

Bone marrow stem cells are the factories that produce new T-cells. But rather than simply genetically modifying T-cells, Ribas is modifying the bone marrow stem cells that make them. In other words, he’s modifying the car factory, not just the car.

The result, in theory, is a lifetime supply of cancer-fighting T-cells and, hopefully, a more cancer-resistant immune system. Testing that theory will require years of clinical trials. Daniel Apodaca, 25-year-old UCLA student who has epithelioid sarcoma, a rare, soft tissue cancer that grows slowly, became the trial’s first patient in April.

“I didn’t have any options before,” Apodaca told CNNMoney. “So just having an option in general, I feel really lucky.”

Ribas said doctors extracted some of Apodaca’s bone marrow stem cells along with a batch of T-cells and modified them in the lab. Chemotherapy helped eradicate his existing immune system cells, making room for the new and improved ones. The immune system reboot kept Apodaca in a sterile hospital environment for three weeks. When he left on April 24th with his reprogrammed immune system, doctors called it his second birthday. But it will be years before they can definitively say the treatment worked.

Beyond the uncertainty inherent in any experimental treatment, immunotherapies come with risks and side effects, such as colitis, or colon inflammation, infection, or even a severe or fatal allergic reaction, although that’s rare. And cell therapy carries the possibility that the upgraded immune system could attack healthy tissues, said Fred Ramsdell, Vice President of Research at the Parker Institute for Cancer Immunotherapy.

“As we try to amp up the immune system, we do run the risk of having the immune system recognize some of our normal tissues,” and attack them, he said.

If that happens, “we’ll pull the safety mechanism,” Ribas said. “We [insert] a gene that allows us to kill them if they become bad.”

Despite the risk, the therapy could advance the field of immunotherapy, Ramsdell said. “We need to find ways to sustain the effect of adapted cell therapies,” he said. “This trial is pushing the envelope.”

Achieving that progress took more than a decade of research and millions of dollars, Ribas said. The California Institute for Regenerative Medicine, a taxpayer-funded research organization, financed the trial with a $20 million grant.

Ribas estimates the therapy could cost hundreds of thousands of dollars per patient. And even if it works, big questions remain about its wider application. The key to an effective targeted immunotherapy is detecting the unique signature of a patient’s specific cancer and matching it with a receptor that doctors can add to a T-cell. That’s how the modified T-cell knows to attack the cancerous cells, not healthy cells. But the process of matching cancer signatures and receptors has proven difficult, and the list of matches remains relatively short.

“Our first attempt is targeting in particular two cancers, sarcomas and melanomas, because they have a protein called NY-ESO-1 that can be efficiently targeted with a receptor that we have,” Ribas said. “Potentially, we could do more, but every time we use a new receptor we would have to go back to the beginning.”

For now, Apodaca is responding well enough to visit his girlfriend who is finishing up school in Spain. And he manages to stay optimistic about the future. “Hopefully I become the golden child for this amazing scientific movement,” he said. “I look to see some real progress in medicine and for oncology, potentially for all subtypes of cancer.”

That movement remains a long way off. The therapy faces several more clinical trials and rigorous FDA review before it enters widespread use. That is, if it works. And that’s a big if. But such is the nature of medical research. “That’s where we push the limits of science,” Ribas said. “If we don’t do things like this, then we don’t advance.”