Research
Research in our lab focuses on exploiting cutting-edge chemical, biomaterial, and nanomedicine technologies to develop cellular immunotherapies to address unmet clinical needs.
Novel biomaterials for manufacturing and delivering cellular therapies
Chimeric Antigen Receptor (CAR) T cells are T cells genetically engineered to recognize and kill tumor cells. CAR T cell therapy has revolutionized the treatment of some hematological malignancies, and it has the potential to revolutionize the treatment of solid tumors. However, current manufacturing of CAR T cell therapies is costly due to the lengthy (>28 days) manufacturing process which also reduces the quality of the CAR T cells due to extensive ex vivo expansion. The Brudno lab aims to improve the manufacturing of CAR T cells using biomaterials that could shorten the production of CAR T cells from weeks to hours. Our alginate-based, dime-sized scaffolds are capable of manufacturing CAR T cells inside the body to streamline the production of a variety of genetically engineered cells used in immunotherapies. We have shown that biomaterial-produced and delivered CAR T cells have enhanced persistence and potency compared to conventionally-produced and delivered CAR T cells when treating lymphoma, breast cancer, lung cancer, and pancreatic cancer. Our vision is to implant these scaffolds during an out-patient procedure that catalyzes the body to produce its own CAR T cells.
Refillable drug delivery systems
One major direction in the lab centers on developing replenishable drug depots, which allow noninvasive refilling of drug-eluting depots in vivo. We take advantage of nucleic acid binding, bioorthogonal click chemistry, and bio-recognition to capture drug payloads from the blood, including small molecule drugs and nanoparticles. We have demonstrated that replenishable depots can capture therapeutics from circulation. The depot devices retain their ability to capture therapeutics from circulation for months and can be refilled numerous times. More recently, we have created non-toxic, “prodrug” therapeutics that are hydrolytically converted into active molecules inside our refillable devices. The Brudno lab is expanding the replenishable depot technology for use with new chemotherapies such as carboplatin and paclitaxel for targeting locally recurrent peritoneal cancers such as liposarcoma and ovarian cancer. We are also exploring combining replenishable intratumoral depots with blood-brain barrier disruption for targeting gliomas, including glioblastoma. The lab is also actively researching combining replenishable depots with immunotherapy to improve safety and efficacy of this promising technology.
Materials-free drug delivery systems
Sustained, local delivery of therapeutics could revolutionize the care of patients by reducing toxicity and rapid clearance. Unfortunately, existing local delivery technologies require extraneous materials such as scaffolds or implants to be placed at the target site. These materials limit the use of these local drug depots, making them impractical in many parts of the body, including the brain, stiff tumors, fibrous tissues, and joints. Recently our research group developed a novel, materials-free sustained release technology, termed Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). The TRAPs technology takes advantage of tissue structures by attaching drugs through a covalent bond directly at the site of administration. Importantly, the drug is attached via a robust and tunable chemical linker that slowly dissolves, for sustained release into the tissue. Overall, this invention provides a flexible drug delivery platform amenable to many drug classes for the treatment of cancer, infection, inflammation, and many other diseases.