Andreia Maia, Immuno-Oncology Scientist at Dana-Farber Cancer Institute, shared Rizwan Romee‘s, Associate Professor at Dana-Farber Cancer Institute, post on LinkedIn, adding:
“Really happy to share this paper from our lab, led by Mubin Tarannum and Rizwan Romee, now out in Cancer Discovery!
IL-12 is one of the most potent immune-activating cytokines we have, but toxicity has always made it hard to use clinically. So, we tried a different approach: what if we kept it local?
We engineered mesothelin-targeted CAR-NK cells to anchor IL-12 directly in the tumor matrix. This boosted NK cell persistence, metabolic fitness, and cytotoxicity in ovarian and pancreatic cancer models, with mTORC1 as the key node connecting IL-12 and CAR signaling.
Proud to be part of the RomeeLab and Dana-Farber Cancer Institute.”
Quoting Rizwan Romee‘s post:
“Delighted to share our work led by Mubin Tarannum in my lab now online in Cancer Discovery AACR Journals:
‘Spatially confined IL-12 programs CAR-NK cells through mTORC1 to coordinate antitumor immune networks.’
IL-12 is one of the most potent immune-activating cytokines we have, but systemic delivery has long been limited by toxicity. We asked whether confining it to the tumor matrix could unlock its potential without the cost.
Key findings:
- We engineered mesothelin-targeted CAR-NK cells to secrete IL-12 fused to a collagen-binding A3 domain, anchoring the cytokine in the tumor extracellular matrix rather than letting it circulate.
- IL-12 markedly enhanced CAR-NK persistence, metabolic fitness and cytotoxicity in ovarian and pancreatic cancer models independent of exogenous cytokines
- mTORC1 emerged as the integration node where IL-12 and CAR signaling converge – linking the two inputs to the metabolic reprogramming that drives NK cell function.
- Beyond the NK cells themselves, spatially confined IL-12 remodeled the tumor microenvironment and engaged endogenous immune networks, pointing to an effect broader than the infused product alone.
I would also like to thank to our collaborators across Dana-Farber Cancer Institute and Massachusetts Institute of Technology.
More importantly this work is moving into clinic in patients with advanced ovarian cancer in collaboration with Dr Ursula Matulonis and Dr Rebecca Porter at DFCI”
Read the full article:
Article: Spatially confined IL-12 programs CAR-NK through mTORC1 to coordinate antitumor immune networks
Authors: Mubin Tarannum, Khanhlinh Dinh, Mila Stanojevic, Maily Nguyen, Marco Campisi, Andreia Maia, Fuguo Liu, Shaobo Yang, Grace C Birch, Eden Bobilev, Ian Gillanders, Michal Sheffer, Shikha Gupta, Junning Wang, Suthakar Ganapathy, Daniel E Michaud, Guillermo Nicolas Dalton, Seema Chugh, Quang-De Nguyen, Cloud P Paweletz, Prafulla C Gokhale, Yang Gao, Jose Cancelas, Jennifer L Guerriero, Toni K Choueiri, David A Barbie, Andrew J Aguirre, Rebecca L Porter, Ursula A Matulonis, John Koreth, Catherine J Wu, Robert J Soiffer, Jerome Ritz, Jianzhu Chen, Rizwan Romee
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