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Proinflammatory cytokines such as IL12, IL15, and IFN alpha have long been attractive means of armoring cell therapies, but come with risks of uncontrolled distribution and activity. In these posters and publications, I worked at Obsidian Therapeutics to control the expression of those cytokines.
Publications
Patents
Sethi D, Smith SG, Ols M et al. Compositions and systems for regulation of function/abundance and delivery of polypeptide payloads. WO2023069418A2
Posters
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Ovarian cancer remains one of the hardest solid tumors to treat, where durable responses are rare. This work at MIT focused on making better immunotherapy for ovarian tumor through better models and smarter delivery. In collaboration with Sonia Iyer – an incredible PostDoc in Bob Weinberg’s lab - I explored the immune microenvironment of genetically defined syngeneic mouse models built by Sonia. We mapped combination-therapy opportunities and resistance biology to guide rational immuno-oncology pairings. From a delivery perspective I worked with Tony Barberio to engineer tumor-targeted “cell-cancer–coating” liposomal nanoparticle to deliver cytokines such as IL-12 to tumors, improving localization, safety, and antitumor potency. Together, these studies link mechanism, models and materials, advancing a translational path for combination immunotherapy in ovarian cancer.
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Gene therapy for sickle cell disease is curative, but inaccessible to most of the world due to the need for ex vivo manipulation of hematopoietic stem cells. I led a project funded by the Gate’s Foundation during my time at MIT seeing if we could reach the stem cells in the body using targeted lipid nanoparticles - with the long term goal of expanding patient access. I did early work showing that we could conjugate polymer layered liposomal nanoparticles with targeting antibodies and increase targeting in vivo. This generated enough interest to get follow-on funding, but I ultimately left that work to a talented Postdoc (Tamara Dacoba) and PhD student (Namita Nabar) who advanced the concept to two publications. To be clear, these are not my publications, but did came from groundwork I laid. I share them here to demonstrate my continued interest and expertise in the field of targeted LNPs.
Dacoba, T. G.; Nabar, N.; Hammond, P. T. Modular Layer-by-Layer Nanoparticle Platform for Hematopoietic Progenitor and Stem Cell Targeting. ACS Nano. (2025)
Nabar, N.; Dacoba, T. G.; Covarrubias, G.; Romero-Cruz, D.; Hammond, P. T. Electrostatic adsorption of polyanions onto lipid nanoparticles controls uptake, trafficking, and transfection of RNA and DNA therapies. PNAS. (2024)
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Bladder cancer affects ~600,000 people globally each year, and most cases present as non-muscle invasive disease (NMIBC). For more than four decades, intravesical BCG has been the standard of care—effective for many, but limited by high rates of failure and recurrence. My work explores a more targeted immunologic approach: local delivery of interleukin-12 (IL-12) to drive antitumor immunity with the potential for longer-term protection. Using chitosan, a readily available mucoadhesive biopolymer, we improved IL-12 retention and urothelial penetration in the bladder to enhance pharmacology and durability. I remain interested in advancing intravesical immunotherapy. In particular I am interested in leveraging urology’s established, frequent instillation workflows to test timing, sequencing, and next-generation modalities (including gene therapies) that may be too toxic systemically but are well-suited to local delivery.
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The bladder is the least permeable membrane in the human body which presents an opportunity for delivery of toxic compounds directly into the bladder to treat cancer, but also includes challenges in terms of allowing those agents to best perform their activity. This study used modeling to see if simple changes to instillation protocol could help therapeutic agents penetrate deeper into the bladder wall.