Amanda Finck, Postdoctoral Researcher of June Academic Lab at University of Pennsylvania, shared a post on LinkedIn about a recent article she and her colleagues co-authored, adding:
“Paper alert from the June Lab
What if the better answer to solid tumor CAR T cells lies outside the tumor itself?
Here we engineered a bicistronic CAR T cell that targets:
- CD19 on peripheral cells to drive expansion
- A solid tumor antigen to focus effector function where it is needed most
We optimized CAR orientation and signaling domains, ultimately selecting a CD19/28ζ–M5/BBζ configuration that may better recapitulate natural T cell biology, with early 28ζ signaling followed by downstream 4‑1BBζ support.
Next, leveraging immunocompetent mouse models, we demonstrated efficacy, tolerability, and their trafficking patterns over time.
To probe translational potential in a setting that better mirrors human biology, we built a novel system to reconstitute “B cells” in immunodeficient mice that normally lack them.
First, we tested a donor‑matched ‘T‑APC’ strategy, transducing T cells with CD19 antigen (similar to approaches explored clinically in relapsed/refractory CD19 CAR T patients). This increased expansion in vitro and in vivo, but did not fully recapitulate the anti‑tumor efficacy seen in immunocompetent models.
We then expanded donor‑matched B cells, which surprisingly drove both stronger CAR T expansion and superior anti‑tumor activity in vivo, against all in vivo engraftment/trafficking odds.
This unexpected result drives home the role of target cells in imprinting CAR T fate and function.
I believe all good science is team science! Grateful to all of my co-authors: Ziming Wang, Donna Gonzales, Nils Wellhausen, Sofía Castelli, PhD, Esha Banerjee, M. Angela Aznar, and to my mentors Carl June and Regina Young. Special thanks to past and present lab members for the ‘intangibles’ that made my thesis journey both possible and all the more enjoyable.”
Title: Dual-targeted ping-pong CAR T cells: Leveraging peripheral expansion to improve solid tumor immunotherapy
Authors: Amanda V. Finck, Ziming Wang, Donna Gonzales, Nils Wellhausen, Sofía Castelli, Esha Banerjee, M. Angela Aznar, Regina M.Young, Carl H. June
Read the Full Article on PNAS
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