PhD Public Seminar: ANDREA MOLINA
When & Where
July 15
2:00 PM - 3:00 PM
UTHealth Houston, School of Dentistry SOD 4340, Graza Classroom and via Teams (View in Google Map)
Contact
- Joy A. Lademora
- 713-500-9872
- [email protected]
Event Description
Localized Delivery of Combination Immunotherapy for Head and Neck Cancers
Andrea Hernandez Molina, BS (Advisory: Simon Young, DDS, MD, PhD)
Most head and neck squamous cell carcinoma (HNSCC) patients do not respond to single-agent immunotherapy, largely due to the immunosuppressive tumor immune microenvironment (TIME). Therefore, understanding the TIME and tumor-draining lymph nodes is critical for improving immunotherapy responses. Current FDA-approved immunotherapies are administered systemically. Thus, examining circulating immune cells, as well as immune responses in peripheral tissues such as blood and spleen, may provide insights into generating durable systemic immunity. In this dissertation, the tumor immune microenvironment and peripheral immune responses were immune profiled in a clinically relevant HPV-negative orthotopic oral cancer model to identify mechanisms of immunosuppression. The insights from the TIME were leveraged to guide the design and localize delivery of immunotherapies. Then, I applied localized immunotherapy delivery strategies including multiple intratumoral injections of a stimulator of interferon genes (STING) agonist and a single-dose of the STING agonist loaded-dual-biomaterial system in combination with systemic delivery of immune checkpoint inhibitors in the HPV-negative orthotopic oral cancer model. In conclusion, the single-dose of the dual-biomaterial system was able to localize the delivery of the immunomodulator as effectively as the multiple intratumoral injections. Finally, intratumoral delivery of interleukin-12 (IL-12) and systemic anti-programmed cell death protein-1 (α-PD-1) therapies were administered across oral cancer models with varying immune-infiltration to inform context-specific immunotherapy design and application. In summary, understanding the dynamic composition of the TIME and host immune response during disease progression will guide the selection of combination therapies and effective delivery approaches.
Advisory Committee:
- Simon Young, DDS, MD, PhD, Chair
- Zhiqiang An, PhD
- Mary Farach-Carson, PhD
- Jeffrey Hartgerink, PhD
- Andrew Sikora, MD, PhD
Localized Delivery of Combination Immunotherapy for Head and Neck Cancers
Andrea Hernandez Molina, BS (Advisory: Simon Young, DDS, MD, PhD)
Most head and neck squamous cell carcinoma (HNSCC) patients do not respond to single-agent immunotherapy, largely due to the immunosuppressive tumor immune microenvironment (TIME). Therefore, understanding the TIME and tumor-draining lymph nodes is critical for improving immunotherapy responses. Current FDA-approved immunotherapies are administered systemically. Thus, examining circulating immune cells, as well as immune responses in peripheral tissues such as blood and spleen, may provide insights into generating durable systemic immunity. In this dissertation, the tumor immune microenvironment and peripheral immune responses were immune profiled in a clinically relevant HPV-negative orthotopic oral cancer model to identify mechanisms of immunosuppression. The insights from the TIME were leveraged to guide the design and localize delivery of immunotherapies. Then, I applied localized immunotherapy delivery strategies including multiple intratumoral injections of a stimulator of interferon genes (STING) agonist and a single-dose of the STING agonist loaded-dual-biomaterial system in combination with systemic delivery of immune checkpoint inhibitors in the HPV-negative orthotopic oral cancer model. In conclusion, the single-dose of the dual-biomaterial system was able to localize the delivery of the immunomodulator as effectively as the multiple intratumoral injections. Finally, intratumoral delivery of interleukin-12 (IL-12) and systemic anti-programmed cell death protein-1 (α-PD-1) therapies were administered across oral cancer models with varying immune-infiltration to inform context-specific immunotherapy design and application. In summary, understanding the dynamic composition of the TIME and host immune response during disease progression will guide the selection of combination therapies and effective delivery approaches.
Advisory Committee:
- Simon Young, DDS, MD, PhD, Chair
- Zhiqiang An, PhD
- Mary Farach-Carson, PhD
- Jeffrey Hartgerink, PhD
- Andrew Sikora, MD, PhD