Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer

Author:

Som Avik12ORCID,Rosenboom Jan‐Georg1234ORCID,Wehrenberg‐Klee Eric1,Chandler Alana2,Ndakwah Gabrielle2,Chen Eric2,Suggs Jack2,Morimoto Joshua2,Kim Jonathan1,Mustafa Abdul Rehman1,Marcos‐Vidal Asier1,Fintelmann Florian J.1,Basu Arijit2,Langer Robert235,Traverso Giovanni245ORCID,Mahmood Umar1

Affiliation:

1. Department of Radiology Division of Interventional Radiology Massachusetts General Hospital Boston MA 02114 USA

2. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA 02139 USA

3. Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA

4. Division of Gastroenterology Brigham and Women's Hospital, Harvard Medical School Boston MA 02115 USA

5. Department of Mechanical Engineering Massachusetts Institute of Technology Boston MA 02139 USA

Abstract

AbstractPercutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the “abscopal” effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel‐based controlled release formulation is developed for the FDA‐approved Toll‐like‐receptor 7 (TLR7) agonist imiquimod (“Imigel”) that forms a tumor‐resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly‐lactic‐co‐glycolic acid‐polyethylene glycol‐poly‐lactic‐co‐glycolic acid (PLGA‐PEG‐PLGA)‐based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo‐antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio‐opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90‐day survival studies.

Funder

Deshpande Center for Technological Innovation, Massachusetts Institute of Technology

National Cancer Institute

Radiological Society of North America

National Institutes of Health

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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