From the Lab to the Clinic: Hasan Ready to Translate Her Photodynamic Research into Patient Care

After nearly four decades of developing light-based technologies for treating disease at Massachusetts General Hospital, Tayyaba Hasan, PhD is excited about the potential to turn her discoveries into new treatments for patients.

“We’re at a good place scientifically with this light-triggered nanotechnology, where the light is an agent that provides something unique,” Hasan says. “It becomes an enabler of conventional treatments and also becomes a unique treatment by itself.”

These projects include a nanotechnology platform to deliver combination therapy for cancer patients, as well as low-cost technologies for treating oral cancer and testing for antibiotic resistance in resource-limited settings across the globe.

An investigator at the Wellman Center for Photomedicine, a professor of dermatology at Harvard Medical School and a professor of health sciences and technology at Harvard-MIT, Hasan is eager to collaborate with industry to move these projects further down the pipeline to commercialization. She has been working with the Partners Innovation team to connect with potential partners.

What is photodynamic therapy (PDT)?

Photodynamic therapy (PDT) uses low-frequency light in conjunction with light-sensitive molecules to provide imaging and diagnostic information and/or deliver therapies to harmful cells or microbes in the body.

In a typical use case, the molecules are engineered to seek out targets of interest (cancer cells, for example). When they reach their target, a tissue-penetrating light is administered to the patient, which activates the molecule, causing it to produce light for imaging or diagnostics or to start a treatment.

Hasan first demonstrated success using this technique in the mid-1990s when her lab developed a simplified light-based nanotechnology platform to treat age-related macular degeneration (AMD). The treatment was brought to market in the early 2000s by Novartis under the trade name Visudyne and has since been used to treat millions of AMD patients.

Combination therapy for cancer

Combination therapy is a rapidly developing strategy for treating cancer with multiple drugs to target different cell types in the tumor. A key challenge with current treatment methods is timing, Hasan explains. Typically, each drug is given by separate injections, and they often don’t work in concert. “If you inject drug A and then drug B, each has its own pharmacokinetics and will reach the target at different times.”

The ability to deliver treatments simultaneously is a key strength of the platform developed in Hasan’s lab. The platform is essentially a lipid bag that can be filled with multiple drugs. The bag itself is encircled by a light-activated molecule, which is engineered to target tumor cells.

When activated by light, the molecules break apart, causing a chemical reaction that starts to kill cancer cells on its own. This initial treatment also opens up channels that allow the drugs within the lipid bag to penetrate into the tumors. Since the treatment can be modified to deliver a variety of drugs, it could be applied to a variety of cancers, including glioblastomas and ovarian and pancreatic cancer.

“This one is on our priority list to get into the clinic,” Hasan says. “The limitation there is just funding. How do you get it made using good manufacturing processes (GMP) so it can be injected into patients?”

A cost-effective treatment for oral cancer

Another key focus area in Hasan’s lab is the development of low-cost technologies to solve pressing health issues in resource-limited countries.

In a project funded by the National Institutes of Health (NIH), she has developed and validated a light-based treatment for oral cancer patients in India where the disease is a huge public health problem.

In a collaboration with one of Hasan’s former postdocs—who is now a professor at the University of Massachusetts—Hasan created three-dimensional printed light applicators that can be custom-fitted to the mouths of oral cancer patients.

The light-activated molecules, which are designed to target cancer cells, are administered to patients by drinking a glass of orange juice. Prior to starting the treatment, the team can scan the mouth with a smartphone to locate the tumor via fluorescent imaging. The treatment can then be activated by shining light through the 3D applicator, which the patient bites down on.

The team has treated 21 patients so far, and 18 of those have been disease-free after only one three-hour treatment. “That is huge for India because, conventionally, what they do is chemotherapy, surgery, or radiation,” Hasan says. “These treatments can impair eating habits, put you out of work, and make you very ill, and these people can’t afford to take time off.”

Testing for antibiotic resistance

In a second project in Thailand, Hasan and her team are developing a light-based technique for detecting antibody resistance.

She explains that many resource-limited countries don’t have the full range of antibiotics that are available in the U.S. “They have four or five antibiotics, and you’ve got to figure out which one is going to work,” Hasan says. “Otherwise, if you wait for two days to look at the effectiveness of the treatment, it could be too late—the bacteria multiply very fast.”

Hasan and her team have designed a probe in which the molecules are designed to stay dark until they encounter bacteria expressing an enzyme called b-Lactamase, an indicator of resistance. The molecule then lights up indicating that the antibiotic being tested is not going to effective.

Partnering with Innovation

“Right now, it seems like Partners Innovation is the best it’s ever been,” she says. “It’s expanded considerably, and there is better interaction with investigators. I think that’s terrific.”