Super excited to share our recent work now out in @Nature! We introduce trans-synaptic tracing tools from circuit neuroscience to study the whole-brain connectome of glioblastoma. nature.com/articles/s4158…
Thrilled to share our new preprint! We leverage GBM organoids and monosynaptic rabies tracing to reveal the brain-wide connectome of this cancer, including a cholinergic neuron-tumor synapse that may fuel GBM invasion. @UPenn_SongMing#CancerNeuroscience
We hope this study provides new tools for the study of #CancerNeuroscience and may eventually lead to a better understanding of this devastating disease.
Monosynaptic herpes simplex virus tracing, immuno-electron microscopy, and functional assays all confirm a cholinergic neuron-to-glioma synapse. Acetylcholine may play a role in GBM invasion via the CHRM3 receptor, which is a potential therapeutic target.
By transplanting glioblastoma organoids and performing monosynaptic rabies virus tracing, we find rapid and extensive brain-wide circuit integration of GBM. GBM inputs are highly diverse and include, for example, long-range cholinergic neurons from the basal forebrain.
We generated GBOs in tandem with our phase 1 trial of bivalent CAR-T cells in recurrent GBM (doi.org/10.1038/s41591…) and treated them with patient CAR-T cells. We found that cytolysis and cytokine release mirrored patient responses, highlighting the potential of this platform.
Check out the preprint for our new study on the temporal dynamics of CAR-T cells with GBM organoids, mapped in exquisite detail! Congrats @danzhang122!!
So excited to share this study looking at the dynamic interplay between GBM and CAR T cells during treatment using organoids and single cell multi-omics! Hopefully this moves us toward a better understanding of #immunotherapy in #GBM. Huge thanks to @UPenn_SongMing@DrORourke2!