Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment

Author:

Moreau Michele12ORCID,Keno Lensa S.13,China Debarghya1ORCID,Mao Serena1,Acter Shahinur1ORCID,Sy Gnagna1ORCID,Hooshangnejad Hamed1ORCID,Chow Kwok Fan2,Sajo Erno2ORCID,Walker Jacques4,Oh Philmo4,Broyles Eric4,Ding Kai1ORCID,Viswanathan Akila1,Ngwa Wilfred12

Affiliation:

1. Department of Radiation Oncology and Molecular Radiation Sciences, Department of Biomedical Engineering, Johns Hopkins Hospital, Baltimore, MD 21287, USA

2. Department of Chemistry and Department of Physics (Medical Physics), University of Massachusetts Lowell, Lowell, MA 01854, USA

3. Department of Health Administration and Human Resources, The University of Scranton, 800 Linden Street, Scranton, PA 18510, USA

4. Nanocan Therapeutics Corporation, Princeton, NJ 08540, USA

Abstract

Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

Funder

National Institutes of Health

Publisher

MDPI AG

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