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Michelle Dion




Research Fellow




PhD NSF Research Fellow




Michelle Z. Dion*, Safwan Alomari, Pere Dosta, Daniel Dahis, Alex Cryer, Nuria Puigmal, Ivana Ling, Sofia Carrasco, Henry Brem, Betty Tyler, Natalie Artzi

Engineering therapeutic immunity to glioblastoma through the locoregional delivery of chemoimmunotherapy using adhesive hydrogels

I am a fourth-year PhD candidate in the HST MEMP program at MIT/HMS. We are creating a startup based on my PhD work on adhesive hydrogel therapies for brain cancer, highlighting my focus on translational research. I intend to continue my training as a postdoc in immunoengineering, aiming to build my academic lab at the interface of biomaterials, systems immunology, and synthetic biology with the goal of engineering complex cellular systems therapies in vivo. Interacting with clinicians, scientists and entrepreneurs at WMSS would help me identify new collaborators and mentors that could help me achieve my research and career goals.

Background: Despite its promise, immunotherapy shows limited efficacy in glioblastoma because of its poor therapeutic delivery to target tissues and the inability of monotherapy to overcome glioblastoma’s immune evasiveness and rapid growth. Here, we developed a local hydrogel chemoimmunotherapy (doxorubicin, cyclic dinucleotide) to concurrently eliminate tumor cells while generating a multifaceted tumor-specific immune response to prevent tumor growth and recurrence.

Methods: Therapeutic efficacy was evaluated by assessing tumor growth kinetics and survival in orthotopic, syngeneic tumor-bearing mice (GL261). All mice demonstrating long-term survival (>60 days) were rechallenged contralaterally to assess immune memory. Immunophenotyping (flow cytometry, ELISA) was performed to evaluate therapy-induced anti-tumor immune responses on Days 2 and 7. Drug delivery profiles were characterized using IVIS fluorescence imaging.

Results: The local administration of a single dose of hydrogel chemoimmunotherapy resulted in curative survival in over 90% of treated mice, stimulated potent multi-axis anti-tumor immune responses, induced immunological memory that prevented tumor regrowth upon rechallenge, and was well-tolerated. In comparison, intravenous or intratumoral delivery of free therapies did not improve survival. 

Conclusions: This study demonstrates the therapeutic potential and significant immunomodulatory effects of local sustained delivery of cyclic dinucleotides in combination with immunogenic chemotherapy for the treatment of glioblastoma.