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Fabrication and Characterization of Tumor Nano-Lysate as a Preventative Vaccine for Breast Cancer
Jenna A Dombroski1, Nidhi Jyotsana1, Davis W Crews1
1Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.
Abstract:
Breast cancer is the most common cancer among women in the United States, with late stages associated with the lowest survival rates. The latest stage, defined as metastasis, accounts for 90% of all cancer-related deaths. There is a strong need to develop antimetastatic therapies. TRAIL, or TNF-related apoptosis inducing ligand, has been used as an antimetastatic therapy in the past, and conjugating TRAIL to nanoscale liposomes has been shown to enhance its targeting efficacy. When circulating tumor cells (CTCs) released during metastasis are exposed to TRAIL-conjugated liposomes and physiologically relevant fluid shear stress, this results in rapid cancer cell destruction into cell fragments. We sought to artificially recreate this phenomenon using probe sonication to mechanically disrupt cancer cells and characterized the resulting cell fragments, termed "tumor nano-lysate", with respect to size, charge, morphology, and composition. Furthermore, an in vivo pilot study was performed to investigate the efficacy of tumor nano-lysate as a preventative vaccine for breast cancer in an immunocompetent mouse model.
Insights
This study developed "tumor nano-lysate" from breast cancer cells, mimicking a natural cell-killing process. This nano-lysate shows promise as a novel preventative breast cancer vaccine.
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Breast cancer metastasis is a leading cause of cancer-related deaths, necessitating novel antimetastatic therapies.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows antimetastatic potential, enhanced by nanoscale liposome conjugation for improved targeting.
- Natural processes involving TRAIL-conjugated liposomes and shear stress rapidly destroy circulating tumor cells (CTCs).
Purpose of the Study:
- To artificially replicate the rapid destruction of cancer cells using mechanical disruption.
- To characterize the resulting cell fragments, termed "tumor nano-lysate."
- To evaluate the potential of tumor nano-lysate as a preventative breast cancer vaccine in vivo.
Main Methods:
- Utilizing probe sonication to mechanically disrupt breast cancer cells, creating tumor nano-lysate.
- Characterizing the physical and compositional properties of the generated tumor nano-lysate (size, charge, morphology).
- Conducting an in vivo pilot study in an immunocompetent mouse model to assess vaccine efficacy.
Main Results:
- Successfully generated and characterized tumor nano-lysate with specific physical and compositional attributes.
- Demonstrated the potential of tumor nano-lysate to serve as a preventative vaccine against breast cancer in a preclinical mouse model.
Conclusions:
- Tumor nano-lysate represents a novel therapeutic strategy derived from mechanically disrupted cancer cells.
- This approach holds promise for developing new antimetastatic therapies and preventative cancer vaccines.
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