Interventional Oncology
Eric Wehrenberg-Klee, MD
Faculty
Massachusetts General Hospital
Jan-Georg Rosenboom, PhD
Post-doctoral Scientist
MIT
Alana Chandler, B.S.
Student
MIT
Gabrielle Ndakwah, B.S.
Student
MIT
Jonathan Kim, n/a
Student
MGH
Vivian Feig, PhD
Post-doctoral Scientist
BWH
Asier Marcos-Vidal, PhD
Post-doctoral Scientist
MGH
Florian J. Fintelmann, MD
Faculty
MGH
Arijit Basu, PhD
Post-doctoral Scientist
MIT
Robert Langer, PhD
Professor
MIT
Giovanni Traverso, MD, PhD
Faculty
BWH
Umar Mahmood, MD, PhD
Professor
MGH
Intratumoral immunoadjuvant injections using image-guidance are an area of significant clinical interest, but current therapies suffer because they need frequent injections as well as their inability to confirm target delivery. Developing controlled release and imageable formulations of injectable immunoadjuvants will greatly improve the clinical translation of these therapies for intratumoral immunotherapy. To address this shortcoming, we have developed and evaluated an injectable hydrogel-based controlled release formulation for the FDA-approved drug imiquimod (“Imigel”) with a drug concentration and release profile that mimics an entire multi-day course of therapy with a single injection.
Materials and Methods:
All animal studies were approved by the IACUC. Imigel was developed utilizing a combination of previously clinically used PEG based excipients combination with the FDA-approved drug imiquimod. The gel was tested for injectability, shear stress, viscosity, and controlled release ex vivo. Radio-opacity in vivo was evaluated in combination with iopamidol via micro-CT. Using two checkpoint inhibitor (CPI) resistant metastastic tumor murine model mimics, we evaluated for 90 day survival after intratumoral imigel injection with and without cryoablation. Tumors post injection were subsequently also evaluated by flow cytometry and immunofluorescence for markers of immune activation.
Results:
Imigel demonstrated good injectability and depot formation with a temperature sensitive gelation in vivo versus being liquid at room temperature, as well as being radio-opaque when combined with iopamidol. The addition of intratumoral Imigel to systemic CPI significantly increases 90 day survival to 46% (6/13) compared to CPI alone 0% (0/10) (p=.0045 Log Rank Test), and maintains this effect with combination cryoablation. This corresponded to an increase in activated CD8 T-cell activity seen in the non-treated tumor compared to control (p=.03).
Conclusion:
Because imigel uses FDA and clinically approved compounds and excipients, this platform may provide a rapidly translatable adjunct for patients with metastatic disease via image-guided (ultrasound and computed tomography) interventional therapies.
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