Oncology seminars

Gladstone-UCSF Institute of Genomic Immunology Seminar by Christine Brown, PhD (Deputy Director, T Cell Therapeutics Research Laboratories) on developing and refining redirected CAR T cells for malignant brain tumors, including glioblastoma, tumor heterogeneity, immunosuppressive microenvironments, delivery routes, and manufacturing.

Gliomas are brain tumors formed by networks of connected tumor cells, nested in and interacting with neuronal networks. Neuronal activities interfere with tumor growth and occurrence of seizures affects glioma prognosis, while the developing tumor triggers seizures in the infiltrated cortex. Oncometabolites produced by tumor cells and neurotransmitters affect both the generation of epileptic activities by neurons and the growth of glioma cells through synaptic-related mechanisms, involving both GABAergic / Chloride pathways and glutamatergic signaling. From a clinical sight, epilepsy occurrence is beneficial to glioma prognosis but growing tumors are epileptogenic, which constitutes a paradox. This lecture will review how inhibitory and excitatory signaling drives glioma growth and how epileptic and oncological processes are interfering, with a special focus on the human brain.

Observational data have become a popular source of evidence for causal effects when no randomized controlled trial exists, or to supplement information provided by those. In practice, a wide range of designs and analytical choices exist, and one recent approach relies on the target trial emulation framework. This framework is particularly well suited to mimic what could be obtained in a specific randomized controlled trial, while avoiding time-related selection biases. In this abstract, we present how this framework could be useful to emulate trials in malignant melanoma, and the challenges faced when planning such a study using longitudinal observational data from a cohort study. More specifically, two questions are envisaged: duration of immune checkpoint inhibitors, and trials comparing treatment strategies for BRAF V600-mutant patients (targeted therapy as 1st line, followed by immunotherapy as 2nd line, vs. immunotherapy as 2nd line followed by targeted therapy as 1st line). Using data from 1027 participants to the MELBASE cohort, we detail the results for the emulation of a trial where immune checkpoint inhibitor would be stopped at 6 months vs. continued, in patients in response or with stable disease.