SBME Research Seminar - Dr. Hannah Carter
Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. We used machine learning to predict ICB response from germline and somatic biomarkers and studied feature usage by the learned model to uncover putative mechanisms driving superior outcomes. Patients with higher T follicular helper infiltrates were robust to defects in the class-I Major Histocompatibility Complex (MHC-I). Further investigation uncovered different ICB responses in MHC-I versus MHC-II neoantigen reliant tumors across patients. Despite similar response rates, MHC-II reliant responses were associated with significantly longer durable clinical benefit (Discovery: Median OS=63.6 vs. 34.5 months P=0.0074; Validation: Median OS=37.5 vs. 33.1 months, P=0.040). Characteristics of the tumor immune microenvironment reflected MHC neoantigen reliance, and analysis of immune checkpoints revealed LAG3 as a potential target in MHC-II but not MHC-I reliant responses. This study highlights the value of interpretable machine learning models in elucidating the biological basis of therapy responses.
Events
Calendar
- This event has passed.
Research Seminar: Balancing performance and degradation of RNA nanoparticles through targeted changes in ionizable lipid molecular structure – Dr. Omar F. Khan
September 28, 2023 @ 11:00 am - 12:00 pm PDT
Balancing performance and degradation of RNA nanoparticles through targeted changes in ionizable lipid molecular structure
Dr. Omar F. Khan | Institute of Biomedical Engineering; University of Toronto
Talk Description:
Ionizable lipid are combined with excipients and nucleic acids to form lipid nanoparticles. The molecular design of these ionizable lipids have an incredible impact on the performance of the resulting lipid nanoparticles. In this talk, I will discuss how my lab incorporates supramolecular, biomaterial and immunological concepts into our design process to create chemically diverse and efficacious ionizable lipids. Using both rational design and structure-function studies, I’ll review how my group has successfully used internal molecular motifs, noncovalent binding and heteroatomic positioning to control payload capacity, mRNA expression, safety, pharmacokinetics and stability. As an accessible (and enjoyable) introduction to chemistry, biomaterial and immunology concepts, this talk will also illustrate how seemingly disparately fields can be effectively integrated through engineering.
Location:
Life Sciences Institute
Lecture Theatre 1003 (LSC 1003)