Drug Delivery Directly to the Tumor

Historically, scientists have thought of cancer cells as a clone army—since they are all genetically identical, they are universally bad actors.

“What we’ve learned since then is that they are more like special forces,” says David Ting, MD, Assistant Physician at the Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School. “Some are spreading throughout the body, some are replicating, some are doing both and others are doing nothing.”

With a growing understanding of the different roles of cancer cells, Ting and colleagues are developing new treatment strategies that account for this complexity.

It’s an effort that spans the laboratory, the clinic and the marketplace—and one that may require a paradigm shift away from therapies that seek to treat cancer by targeting the genetic mutation alone.

“I think that’s where we’re coming back to now,” Ting says. “A single drug is not enough, so we have to start giving four or five drugs.” This multidrug approach is similar to those taken in treating other disease, he notes.

“In cardiology, you take an aspirin, a beta blocker, an ace inhibitor and some other blood pressure medication. That’s normal. That’s five drugs. And people live with stable cardiovascular disease for many years on that. So, that should be the same for cancer.”

Ting’s research and strategy includes sponsored research agreements, identifying and protecting IP, negotiating the transfer and use of that IP, and, in the case of a new company that Ting is currently developing in stealth mode, with startup funding via the Partners Innovation Fund.

Whether he’s working as a clinician, researchers or entrepreneur, Ting’s focus remains the same. “I went to medical school to take care of people. It’s a great motivator to me. When I start projects or companies, the goal is, ‘How am I going to help the patient?’ That’s all that really matters.”

 

Rethinking Drug Delivery

One key challenge that Ting is working to overcome is drug delivery. Most chemotherapy drugs are delivered intravenously, which means they often have to travel a long way through the body to reach the cancer cells and can cause a lot of collateral damage along the way.

An approach that Ting first started to develop as a postdoc at MIT seeks to move the site of the treatment to the tumor itself. Ting and colleagues have created a flexible, drug-infused polymer patch that can be inserted into the body via laparoscopic surgery and attached to the tumor itself.

This approach would not only ensure that the drugs reach their target but could also make it possible to give patients larger doses since there is less concern about system-wide toxicity.

Ting and colleagues established a company, PanTher Therapeutics, to continue developing this concept and bring it into the market. The company, which is led by Laura Indolfi, PhD, a former postdoc in Ting’s lab, is about to start phase 1 clinical trials.

“I think there are certain cancers that this local delivery approach is highly relevant for,” says Ting. “This includes pancreas cancer, esophageal cancer and potentially mesothelioma—the ones we can’t get drugs into very well.”

 

Potential Applications for the Patch

Pancreatic cancer is particularly difficult to treat due to its location at the center of the body and its proximity to other major organs and vessels. In many patients, the tumors are too intertwined with surrounding blood vessels to be safely removed.

Ting was part of an MGH research team that recently demonstrated success using a multidrug approach to treat pancreatic cancer patients with inoperable tumors. Using a combination of chemotherapy, blood pressure medication and radiation, the team was able to shrink many of the tumors to the point where they could be surgically removed.

However, the process includes giving patients huge amounts of system-wide chemotherapy (eight cycles in four months) followed by radiation and then surgery, which can take a toll on the body. Ting is hopeful that a patch-based approach could make the process easier on patients.

“What if some of the chemotherapy agents could be put directly on the tumor and be released slowly over the course of eight weeks?” Ting says. “We wouldn’t have to give it by IV and it wouldn’t have to hit every cell in your body.”

This direct approach could also work for drugs that have been shown to kill cancer cells but are too toxic for patients to take systemically. If these drugs—many of which have $50 million to $100 million already invested in their development—could be delivered locally, patients may be able to tolerate them, Ting says.

The third, and perhaps most ambitious, potential use of this patch-based approach would be in conjunction with immunotherapy treatments for pancreatic cancer.

In this case, the patch could be used to deliver cytokines that are designed to attract T-cells that have been removed from the patient and genetically modified to recognize cancer cells directly to the cancer site.

“You’re painting the target with all this cytokine storm stuff that is right on the tumor; that says ‘T-cells please come here and kill me.’ That’s probably going to work better if you can stick it on the tumor rather than injecting it.”