Researchers looking to develop cancer treatments inevitably run into one major problem: everything about cancer is unpredictable. Cancers metastasize differently, and even within one specific type, each tumor varies. And patients vary widely, too. 

As a result, it’s challenging to predict which therapeutic treatments will be effective for a unique patient, especially approaches that leverage the immune system. The Institute of Biology, Engineering, and Medicine’s (I-BEAM) Anti-Cancer Immunoengineering Collaborative is working to tackle this challenge in collaboration with the Legorreta Cancer Center at Brown University. 

One of the team’s lead researchers, Dr. Ian Wong, described their work in two key questions: “given that patients are different — and within tumors there’s a lot of complexity — can we predict how a given patient will respond using patient cells?” and “can we engineer and augment immune cells to be more effective?”

Teamwork makes the dream work

Brown is the perfect incubator to cultivate scientists with a fondness for collaboration and translational research. The community is “much more collegial and less siloed” than other institutions, Dr. Wong noted. 

“There is already a strong clinical and basic biomedical research side at Brown,” Dr. Wong said. With the development of I-BEAM’s Collaboratives — working groups composed of scientists from the School of Engineering and the Legorreta Cancer Center — Brown’s researchers have been given a new avenue for formal collaboration.

The Anti-Cancer Immunoengineering Collaborative is “assembling the Avengers in cancer and bioengineering research,” Dr. Wong said, and taking advantage of new hires bringing unique expertise to Brown. 

The Collaborative features team members with engineering expertise like Dr. Theresa Raimondo — who Dr. Wong called an “expert on using RNA to reprogram immune cells” — and Dr. Tejal Desai — whose understanding of drug delivery has helped her “come up with ways to programmably activate immune cells.”

Lead researcher Dr. Patrycja Dubielecka-Szczerba’s lab focuses on blood cancers, and through her work, she has developed a “unique understanding of the response of the cancer macroenvironment.” She knows how cancer cells and the body play off one another, and brings a systemic understanding of cancer to the team. 

Exciting collaborations have emerged including a micro-RNA therapeutic discovered in the El-Deiry Lab and through recent collaborative studies with the Raimondo Lab has been encapsulated for more efficient in vivo delivery. This has led to ongoing studies to improve formulations as well as in vivo studies during the summer of 2025 that already demonstrate target anti-tumor engagement. This work supported by a Sponsored Research Agreement between SMURF-Therapeutics, Inc founded by El-Deiry at Brown and Brown University is demonstrating the power of interdisciplinary collaboration to moving basic and translational science towards commercialization. Grant have been submitted, are being submitted and patent disclosures and filings have been made and are in process.

Programming “immune cells to not get hijacked”

Together, the team is working on new ways to program immune cells to more effectively respond to immunotherapy and mechanisms to enhance drug delivery. Dr. Wong has developed ways to study cancer by growing tumor cells on a dish, seeing how they respond to drugs, and watching how they deform their surroundings. 

Looking at the example of breast cancer, common sites for metastasis include the bone, lung, and liver. All three areas have very different characteristics, and “we still don’t understand why a given patient’s cells will spread to these different sites that are completely different” than the original location in the mammary glands, Dr. Wong said. 

Understanding how cancer behaves differently in each of these locations is key to developing better treatments. Preliminary research has shown that some non-oncology drugs can enhance treatments, Dr. Wong said, but results vary widely based on the location of the cancer. 

By understanding cancer behavior, the team is hoping to predict how patients will respond to treatment. Then, they will work to develop new patient-specific avenues to increase the efficacy of immunotherapy. The eventual aim is to program “immune cells to not get hijacked” by cancer cells, Dr. Wong said. 

Currently, the team is focusing on cancers that fall within their specific areas of expertise and disproportionately impact the local Rhode Island population. “We prioritize through the prism of the population that we are to serve immediately,” Dr. Dubielecka-Szczerba said. “We are working on the global questions and we are trying to bring them back to the local communities and to the hospitals.”

As a result, the team’s focus includes bladder, rectal, and brain cancers, which are “more prevalent in Rhode Island” Dr. Wong said. 

Since Dr. Dubielecka-Szczerba has extensively studied blood cancers, the team is also researching those conditions. As those cancers are “liquid and are a little more accessible,” they can be a good jumping off point for research that can then be extrapolated to other types of cancer, Dr. Dubielecka-Szczerba said.

There is a strength at the Legorreta Cancer Center at Brown through work in the El-Deiry Lab that has discovered and helped develop a novel drug called TIC10/ONC201/Dordaviprone, on the path to FDA approval for treatment of some of the most aggressive brain cancers. As this drug stimulates the innate immune system and triggers anti-cancer stress response pathways, studies within the I-BEAM and Legorreta Cancer Center collaboration have involved studies to investigate the impact of the tumor microenvironment with its complex cellular subtypes through bioengineered scaffolds on drug-induced effects on different cell types that are relevant to the cancer biology and therapeutic responses. The group leverages strengths with focus on Natural Killer cells, T-cells, macrophages, mouse models to derive informative, complementary engineered systems to address complex cellular interactions, soluble factors and drug effects.

In yet other emerging collaborative studies between I-BEAM and the Legorreta Cancer Center, work at published by first author Jillian Strandberg, a PhD graduate student in Biomedical Engineering at Brown, in the Journal of Clinical Investigation in March of 2025 has motivated collaborative directions to model organs-on-a chip to investigate the mitigation of cancer therapy induced lung, skin or esophageal injury as the El-Deiry Lab recently demonstrated in vivo using different genetically engineered mouse strains. 

Approaching cancer “from the systemic perspective”

The team’s research also focuses on approaching cancer systems “from the systemic perspective,” Dr. Dubielecka-Szczerba said. “We tend to look at the cancer as if this is the unit that arose and it doesn’t have any context, and yet it does.”

By studying “the changes of the tumor macroenvironment for any type of tumors systemically,” researchers can better understand how to manipulate cell responses to cancer, Dr. Dubielecka-Szczerba added. 

Another focus is looking at how cancer behaves as patients age. Over time, “the system wears off,” and the damage the body accumulates makes it harder to respond to cancer, Dr. Dubielecka-Szczerba said. Chronic inflammation associated with aging also impacts treatment efficacy. 

As the team’s work progresses, they are faced with challenges accessing necessary funding and “getting pulled in many different directions” Dr. Wong said. While they have identified several target areas for their work, they still need more clinical samples — and more dollars to finance that work, which they envision will lead to breakthroughs to benefit patients in Rhode Island and beyond.

“Without this, we will not be able to develop new avenues and figure out why some of the therapies are not working,” Dr. Dubielecka-Szczerba said.