Postdoc / Research Staff under Giovanni Traverso
Jan-Georg Rosenboom, Avik Som, Eric Wehrenberg-Klee, Alana Chandler, Gabrielle Ndakwah, Jonathan Kim, Vivian Feig, Asier Marcos-Vidal, Florian J. Fintelmann, Arijit Basu, Robert Langer, Giovanni Traverso, Umar Mahmood
Giovanni Traverso, Umar Mahmood
Research Category: Cancer
Systemic treatment with PD-1 and CTLA-4 checkpoint inhibitors (immunotherapy) has been able to cure only a minority of patients with metastatic cancer, given resistance of low-lability metastases to upregulated immune cells. Local intratumoral immune stimulation triggering neo-antigen release and dendritic cell recruitment (e.g., by cryoablation or immunoadjuvant injection) can overcome this barrier to effective immunotherapy. The localized immune response triggering an abscopal effect represents a personalized “cancer vaccine” for a patient’s specific tumor. In our clinical practice (involving intratumoral therapy trials), however, we observe that current therapies suffer from the need for frequent injections as well as their inability to visually confirm target delivery.
To address these shortcomings, we are developing an injectable hydrogel-based intratumoral depot platform for week- and month-long release of existing immunoadjuvants and those in development (e.g. peptides, oncolytic viruses). Our first candidate for low-barrier clinical translation involves FDA-approved imiquimod with a release profile that mimics a week-long daily injection course of therapy with a single injection, paired with CT image-tracking enabled by embedded contrast agents. In dual-tumor model mice, we could show tumor regression in distant tumor metastases and survival (compared with 100% lethality using systemic immunotherapy alone) from a single local depot injection.
Immunotherapy promises a cure for metastatic cancer. However, 80-90% of cancer patients are actually resistant to immunotherapy, and existing systemic immunotherapy has significant side effects. A new paradigm is intratumoral injection of immunotherapy drugs directly into the tumor – acting locally, but triggering a systemic immune response throughout the body. However, current approaches for intratumoral drugs and their clinical trials often fail, particularly because of three main shortcomings: 1) multiple repeated injections are needed, 2) drug leaks away from injection site, and 3) clinicians actually often “miss” as there is no image confirmation of the injected drug.
As experts in controlled release technology and interventional radiology, we are developing an injectable drug depot platform “ImmuGel” that 1) allows controlled drug release over extended periods of time from a tunable polymer network to obviate repeated injections, and 2) allows the clinician to track it via standard CT imaging due to the incorporated contrast agents. This promises to bridge the gaps toward a personalized cancer vaccine for 7 million patients with immunotherapy-resistant metastatic cancers in the US alone.