Projects and Grants per year
Grants and Contracts Details
Description
Abstract: Osteosarcoma is the most common bone cancer in children. The five year survival is currently 70%, and
metastases is the most common complication in the 30% of patients that die of their disease. Preventing and
treating metastases more effectively could significantly reduce the deaths caused by osteosarcoma. Emerging
evidence suggests tumor-associated macrophages are critical to the development of metastases in
osteosarcoma. Usually macrophages are the M1 type and help eliminate cancer cells and prevent metastasis,
however, often these macrophages are re-polarized to M2, cancer promoting macrophages. Our hypothesis is
that re-polarizing M2 macrophages back to cancer eliminating M1 macrophages would prevent metastases. To
re-polarize the macrophages, we have already developed Macrophage derived EngineereD vesicles (MEDs)
from cancer eliminating M1 mouse macrophages and show in our preliminary data these MEDs are able to
convert M2 macrophages to M1 macrophages and that MEDs target specifically to cancers. Since little is
understood about the mechanism underlying macrophage re-polarization by MEDs we will use both experimental
and computational approaches to determine how MEDs interact with macrophages and use this information to
program our next generation of MEDs to have enhanced macrophage re-polarizing properties. These MEDs will
then be tested in our osteosarcoma mouse xenograft models which reliably develop pulmonary metastases to
determine if MEDs can re-polarize tumor associated macrophages in vivo, and if macrophage re-polarization is
an effective strategy for reducing metastases in osteosarcoma. We have also developed human MEDs and will
perform proof of concept studies to assess whether human MEDs can specifically target cancers and re-polarize
macrophages. This work will lay the foundation for a first in human clinical trial of MEDs for the treatment of
osteosarcoma.
Narrative: We have developed mouse Macrophage derived EngineereD vesicles (MEDs) as a therapeutic intervention to
prevent metastases in osteosarcoma and have demonstrated their ability to re-polarize M2 macrophages to the
M1 phenotype in vitro. This proposal will investigate the mechanism by which MEDs re-polarize macrophages,
developed enhanced MEDs and test the ability of these MEDs to re-polarize tumor associated macrophages in
osteosarcoma xenografts. We have also developed human MEDs will determine if human MEDs are able to re-
polarize macrophages. If successful, these experiments lay the foundation for rapid clinical development of
MEDs.
Status | Finished |
---|---|
Effective start/end date | 7/1/22 → 6/30/24 |
Funding
- KY Cabinet for Health and Family Services
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Projects
- 1 Finished
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FY24 Macrophage Derived Engineered Vesicles for Preventing Metastases in Pediatric Osteosarcoma
Kolesar, J. (PI), Badgett, J. (CoI) & Richards, C. (CoI)
KY Cabinet for Health and Family Services
7/1/22 → 6/30/24
Project: Research project