NEAR-INFRARED PHOTOIMMUNOTHERAPY TARGETING OF CANCER-ASSOCIATED FIBROBLASTS
Cancer-associated fibroblasts (CAFs) constitute a prominent cellular component of the tumor stroma, representing a heterogeneous group of activated fibroblasts. Within the tumor microenvironment (TME), CAFs play various pro-tumorigenic roles, including extracellular matrix remodeling, suppression of anti-tumor immunity, and modulation of tumor cell resistance to therapy. Fibroblast activation protein (FAP), a highly expressed marker on immunosuppressive CAFs, has been identified in several epithelial human cancers such as lung, colon, breast, and prostate cancer. Numerous attempts to target FAP+CAFs for inhibiting tumor progression and enhancing anti-tumor immunity have been reported, however, the translation of FAP-directed therapies into human clinical trials has been unsuccessful. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor therapy that utilizes an antibody-photo-absorbing conjugate activated by near-infrared (NIR) light. In this study, we describe the therapeutic efficacy of anti-FAP near-infrared photoimmunotherapy (NIR-PIT) and subsequent immune activation in two immune-competent murine cancer models. Targeting FAP+ cells effectively suppressed tumor growth and reduced lung metastasis in a spontaneous mouse model of mammary cancer. These findings highlight a promising therapeutic approach for selectively and safely eliminating immunosuppressive FAP+ cells within the tumor microenvironment.
Read
- In Collections
-
Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
-
Theses
- Authors
-
Glabman, Raisa A
- Thesis Advisors
-
Hussey, Gisela
- Committee Members
-
Simpson, R. Mark
Agnew, Dalen
Petroff, Margaret
Choyke, Peter
- Date
- 2023
- Subjects
-
Cytology
Veterinary medicine
Immunology
- Program of Study
-
Comparative Medicine and Integrative Biology - Doctor of Philosophy
- Degree Level
-
Doctoral
- Language
-
English
- Pages
- 105 pages
- Permalink
- https://doi.org/doi:10.25335/f5f4-9463