Fighting cancer with cancer: an ‘out-of-the-box’ way to target tumors

The idea seems crazy: inject cancer cells into the bloodstream in order to fight tumors.

It sounds like using a flamethrower to put out a forest fire. But these aren’t just any cancer cells. They’ve been genetically modified to produce a substance that is toxic to tumors.

And because these cells often make a beeline for the cancer from which they came, they can be used as vehicles to deliver their therapeutic payload straight to cancerous masses, slowing down the rate of their growth, and avoiding the toxic effects that cancer-killing chemicals can wreak on the body’s healthy tissues.

In a study published Monday in the Proceedings of the National Academy of Sciences, researchers led by Dr. Wadih Arap and Renata Pasqualini, a husband-and-wife team from the University of New Mexico Cancer Center, provided first proof-of-principle results of this idea of tumor targeting in mouse models of lung, skin, and breast cancer.

“It’s very good science, and it’s out-of-the-box thinking,” said Dr. Tito Fojo, an oncologist at the Columbia University Medical Center, who was not involved in the study. But, he warned, “whether or not it can ever help a patient remains to be seen. It’s worth further investigation.”

The idea of using tumor cells to fight their own kind takes advantage of the wandering nature of this deadly disease.

To some cancer cells, blood vessels are like highways. These cells, known as circulating tumor cells, leave their tumor homes and set out on their own to explore. Some find other organs in which to nestle, forming metastases. But others wend their way back into the tumors from which they first emerged.

Like travelers hardened by life on the road, these “reseeded” tumor cells are thought to be more aggressive than their homebody siblings. They have survived the harsh realities of the outside world, escaping gangs of immune cells and getting themselves out of tight situations. And some oncologists think that these tougher cells are responsible for making tumors grow faster than other tissues.

But the researchers behind the new PNAS study wondered if these loose cancer cells could be used to fight tumors instead of making them stronger. “What if we booby trapped those cells?” asked Pasqualini.

So she, Arap, and their colleagues cultured different kinds of mouse cancer cells in lab dishes, tweaking the genetic code so that the cells produced a substance called TNF, which attacks blood vessels inside tumors. They irradiated these genetically modified cells to ensure they couldn’t proliferate out of control and start forming new tumors, and then injected them into mice with three kinds of cancers — either melanoma, breast, or lung. They found that tumors grew much slower in those rodents, and formed fewer metastases than in other mice that didn’t get the cancer-cell injections.

According to Arap, any kind of cancer therapy could be engineered into the tumor cells in this way. “We used TNF as a proof of concept, but you could use whatever gene you’d like,” he said.

That’s exciting to Dr. Adrienne Boire, an oncologist at Memorial Sloan Kettering Cancer Center. “One wonders what other anti-cancer biologic ‘cargos’ might be delivered to tumors in this manner,” she wrote in an email.

But using cancer cells to deliver treatments also raises a number of potential red flags that makes some doctors and patients uneasy.

“Are you really going to inject tumor cells back into patients?” asked Arap. “And how do you make sure you’re not going to make a bad situation worse?” Arap hopes that he and wife can help answer those questions as the research advances.