Publications by authors named "Bruce D Freimark"
Phosphatidylserine (PS) is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses.
View Article and Find Full Text PDFPurpose: PGN650 is a F(ab') antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer.
View Article and Find Full Text PDFArticle Synopsis
- The study explores the effectiveness of immunotherapy targeting phosphatidylserine in tumors and its combination with anti-PD-1 antibody therapy in breast cancer models, including triple-negative types.
- Experiments on mice with breast tumors showed that the combination treatment not only inhibited tumor growth more effectively but also improved survival rates compared to either treatment alone.
- Results indicated that this combined therapy enhanced immune responses, marked by increased tumor-infiltrating lymphocytes and improved resistance to further tumor challenges, alongside significant changes in immune profile assessments.
Article Synopsis
- Phosphatidylserine (PS) suppresses immune responses in tumor-bearing animals, potentially undermining the effectiveness of immune checkpoint therapies.
- Administering PS-targeting antibodies alongside immune checkpoint inhibitors (CTLA-4 or PD-1) in melanoma-bearing mice significantly improves tumor growth inhibition compared to using either treatment alone.
- The combination therapy also boosts the presence of tumor-infiltrating lymphocytes and enhances proinflammatory cytokine production, indicating a strengthened immune response against tumors.