By now, we were supposed to be able to treat just about every kind of cancer.

President Richard Nixon declared war on the disease in 1971 during his State of the Union speech, pledging to ask Congress for $100 million to find a cure for what was then the second-leading cause of death in America.

“It was thought that we would be able to solve it in about a decade; that was the goal. And we’ve learned over time, cancer is actually much more complex than we gave it credit for in the beginning,” said Gabe Kwong, a Georgia Tech biomedical engineer working toward the goal Nixon laid out more than 50 years ago.

“There are many subtypes of cancer, and each requires a different strategy. And yet, as a population, we’re living longer and longer. People are developing cancers because it’s a disease of aging, basically. So, it’s a big problem, it’s very complex, and it requires new ways of thinking about it.”

Kwong is an associate professor in the Wallace H. Coulter Department of Biomedical Engineering, a joint program shared equally by Georgia Tech and Emory University. For all the reasons he outlined, cancer is a challenging problem.

And who is drawn to big, challenging problems more than engineers?

Kwong’s efforts got a significant boost this fall when President Joe Biden’s Cancer Moonshot Initiative awarded up to $50 million to support a project Kwong has been building to for more than a decade.

He’s assembled a team to develop a new generation of tests capable of detecting multiple types of cancers earlier than ever, allowing doctors to start treatment when tumors are still small and most responsive.

The key is what Kwong calls the Cancer and Organ Degradome Atlas, or CODA platform, which will map the unique cellular profiles of cancer cells and leverage that knowledge to build new bioengineered sensors to detect those profiles.

Cancer ‘Microchips’

In one version, his team used a 3D printer to create a two-step approach: The chip first captured large white blood cells using common proteins on their surface and then used a filter that allowed much smaller red blood cells and platelets through but stopped larger tumor cells. Another approach, called Cluster-Wells, filtered blood to capture tumor cells that have clustered together. They’re more efficient at spreading cancer, Sarioglu said, but also have an interesting biophysical marker — the clumping — that allows him to find them in blood.

“We can design systems that will make sure every cell in that blood sample will go through the same testing. And then you can design a chip that will ‘touch’ essentially each of these cells, pick the ones that are tumor cells, and let the other cells go away,” Sarioglu said. “That way you can actually find a needle in a haystack.”

A Question of Environment

Ankur Singh’s immunoengineering lab is tackling disease disparities for a different cancer. Lymphoma — cancer of the lymphatic system — affects people of all races and ethnicities but occurs in Black patients at a younger age than other groups, and the disease is often more advanced. Black patients also don’t respond to treatment as well as white patients.

Earlier this year, his team published details of a new synthetic hydrogel-based model of the lymphoma microenvironment. They used data from more than 1,100 patients with a specific kind of lymphoma to create their platform, and they were able to grow tumors from patient samples. Singh’s team discovered how the tumors were hijacking the immune system to resist a new kind of inhibitor drug, even at high doses.

“We demonstrated that there is a massive dampening of therapeutic response when you have certain kinds of immune cells present in the tumor microenvironment,” he said. “It is only by using a precision approach of combination therapy that you can overcome those tumors.”

That, he said, is the power of seeing the whole picture: tumor plus its environment. Ultimately, he’s working toward models that could be adjusted to fit every specific tumor and patient to help doctors try treatments before they give them to patients.

“Our approach is that every patient’s tumor is different. Every patient is different. Black patients versus white patients, male versus female, young versus old, obese versus lean, all of those factors are tied into it,” Singh said. “We’re working to make a technology where you can plug-and-play and change the components to meet the needs of that particular patient’s tumor.”

Therapeutic Superhighway

Immunoengineer Susan Thomas also spends her days thinking about lymph nodes.

Thomas specializes in drug delivery — getting therapies to exactly the place they’re needed. And she sees the lymphatic system as the superhighway those therapies can travel.

“When you get vaccinated or have a sore throat, your lymph nodes swell. They’re essentially tissues where tons of immune cells in your body gather. Our thought is to help the magic happen where all the cells are,” said Thomas, professor in the Woodruff School.

Her lab creates biomaterial drug delivery technologies that capitalize on those gatherings. Getting drugs into the lymphatic system means they can reach niches where immune cells gather in high numbers before they distribute elsewhere to fight disease.

“The idea is you want to activate the immune system to go and survey your entire body looking for cancers and then try to kill it,” Thomas said. “And that works for many types of cancer.”

One powerful cancer therapy is a relatively new type of drug called an immune checkpoint inhibitor, which counteracts a trick that tumors play on the body’s immune system. Normally T cells would identify the foreign tumor cells and destroy them. But some tumors produce immune checkpoint proteins, so the T cells think the tumor cells are part of the body and leave them alone.

Immune checkpoint inhibitors essentially block these checkpoint proteins, preventing the tumor from turning off the T cells. Often, though, these therapies work only for a portion of patients. Thomas’ work aims to help those immune checkpoint blockade drugs work better and at a lower overall dose.

“By micro-dosing lymph nodes with those immune checkpoint blockade drugs, you’re getting some of that drug to many cells in one spot. Those cells then leave that lymph node and travel elsewhere in the body. They are now more capable of killing cancer cells, and this was achieved using the drug at a very low dose systemically,” she said.

Traditionally, the approach has been to try to deliver cancer drugs throughout the body or directly to the tumor, she said. “What we’re doing is fundamentally different. We’re trying to get the drug to the immune cell wherever it is, and we think a good place to look is where they naturally congregate — lymph nodes. After interacting with the drug, the immune cell is changed and behaves differently once it is in the tumor. We don’t need the drug to be in the tumor to still have the effects. And we think that is part of the reason why our systems are working so well, because it’s getting more cells to behave in that beneficial, different way.”

Metabolic Machinery

That’s just part of the one-two punch tumors deliver to the body’s metabolism. They also overproduce metabolites, leftovers or byproducts of metabolism. The accumulation of these molecules interferes with T cells, basically turning them off.

Blazeck is working to engineer enzymes to degrade these immunosuppressive metabolites, freeing the T cells to attack the growing tumor.

Right now, he’s exploring both paths in parallel. But the hope is they could eventually converge into a combination approach.

“Our idea to use cells to remodel their metabolic environment hasn’t really been attempted,” Blazeck said. “If we succeed, it would be the first potential way to use an engineered cell therapy to change the extracellular metabolic environment of the cell itself.”

Living Sensors

Blazeck also is part of the multi-institutional research team Gabe Kwong has assembled for his $50 million Cancer Moonshot effort to build an atlas of cancer cell biomarkers and create tests that can detect multiple cancers early in their development.

Kwong has long used cell engineering techniques to create cell therapies or diagnostics. He’s co-founded two biotech companies working to commercialize some of the innovations his team has built in the lab.

Some immune cells do; they patrol the whole body, they can destroy target cells, and some remember once they’ve seen a molecule or antigen. That makes them an exciting potential tool to watch for, produce an alert, and even eradicate cancer lesions early, he said.

“Immune cells have already evolved all these functions. We, as engineers, just need to know how to harness them and redirect — and in some cases, rewire — these functions to do the things that we want the cell to do.”

Helping Families Keep a Watchful Eye

Living biosensors constantly patrolling for cancers would be a game-changer for families who are genetically predisposed to get certain types of the disease. In the meantime, researchers at Georgia Tech, Emory, and the Georgia Clinical & Translational Science Alliance (Georgia CTSA) are working to help these families with a very practical need: keeping track of their intense schedule of tests and doctor appointments.

Roughly 5% to 10% of cancer malignancies occur in patients with cancer predispositions. For these patients and their families, continual surveillance is a fact of life to catch cancer early, when it is most treatable. That means regular blood work, MRIs or other imaging scans, and other procedures.

It can quickly become overwhelming: Because the predisposition is genetic, that usually means everyone in the family is on some kind of testing regimen.

“Keeping track of these appointments is important. We know patients who miss their surveillance studies are worse off from a clinical perspective, and they have a worse prognosis,” said Wilbur Lam, professor in the Coulter Department of Biomedical Engineering and in the Emory University Department of Pediatrics.

Lam leads the innovation catalyst at Georgia CTSA, including AppHatchery, which pulled together clinicians, engineers, and software developers to create a mobile app to help these families avoid the health impacts of missing their regular scans. Called HomeTown, their app is “a simple but elegant solution to addressing a very important clinical problem for these patients,” Lam said.

When Nixon declared war on cancer back in ‘71, it may well have been wishful thinking that scientists would find a cure at all, let alone in a decade.

Susan Thomas argued “cure” isn’t really the goal anyway. She suggested the word “manage” would be more apt — and the tools Georgia Tech engineers are developing will help in that quest.

“In an aging society, you’re going to have a higher prevalence of cancer, not a lower prevalence. What we need to get to is something more like a hip implant: We have tools and we understand how to use them to prolong a healthy and rewarding life for patients.”