Hung Trinh: In Vivo CAR-T Therapy For Inflamm-Aging
Hung Trinh, Senior VP of Operations at Seneca Therapeutics, shared a post on LinkedIn, about a recent article by Zihan Zhang et al, published in Cell Reports Medicine:
“Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in vivo CAR-T therapy for inflamm-aging
Highlights
- Cardiolipin-mimic phosphoramide (CAMP) LNPs transfect T cells without antibody modification
- Circular mRNA prolongs mRNA expression
- Senolytic in vivo CAR-T treats inflamm-aging disease (liver fibrosis and rheumatoid arthritis)
- Develop humanized anti-human uPAR scFv
mRNA-based in vivo chimeric antigen receptor (CAR)-T cell engineering offers advantages over ex vivo therapies, including streamlined manufacturing and transient expression.
However, current delivery methods require antibody-modified vehicles with manufacturing challenges. In this study, inspired by cardiolipin, we identify cardiolipin-like di-phosphoramide lipids that improve T cell transfection without targeting ligands, both in vitro and in vivo. The T cell-favored tropism is likely due to the lipid’s packing, shape, and rigidity.
Encapsulating circular RNA further prolongs mRNA expression in the spleen and T cells. Using PL40 lipid nanoparticles, we deliver mRNA encoding a CAR targeting the senolytic and inflammatory antigen urokinase-type plasminogen activator receptor (uPAR), alleviating uPAR-related liver fibrosis and rheumatoid arthritis (RA).
Single-cell sequencing in humans confirms uPAR’s relevance to senescence and inflammation in RA. To facilitate clinical translation, we screen and humanize single-chain variable fragments (scFvs) against uPAR, establishing a PL40 mRNA-encoded humanized uPAR CAR with potential for treating aging-inflamed disorders.”
Title: Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in vivo CAR-T therapy for inflamm-aging
Authors: Zihan Zhang, Bin Ma, Buyao Li, Zhiwei Li, Min Gao, Hailong Zhao, Rui Peng, Jiang Hu, Yu Wang, Wei You, Xun Gui, Rui Wang, Xiaoqing Hu, Beidi Chen, Yuanjie Zhang, Yanyun Hao, Xiaolin Sun, Peishi Rao, Liang Zhang, Ming Lu, Demin Zhou, Yun Yang, Mi Deng, Lei Miao
Read the Full Artcle on Cell Reports Medicine
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