CAR T cells produced in vivo to treat cardiac injury

Abstract

Making CAR T cells in vivo Cardiac fibrosis is the stiffening and scarring of heart tissue and can be fatal. Rurik et al . designed an immunotherapy strategy to generate transient chimeric antigen receptor (CAR) T cells that can recognize the fibrotic cells in the heart (see the Perspective by Gao and Chen). By injecting CD5-targeted lipid nanoparticles containing the messenger RNA (mRNA) instructions needed to reprogram T lymphocytes, the researchers were able to generate therapeutic CAR T cells entirely inside the body. Analysis of a mouse model of heart disease revealed that the approach was successful in reducing fibrosis and restoring cardiac function. The ability to produce CAR T cells in vivo using modified mRNA may have a number of therapeutic applications. —PNK

Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in Acute Myeloid Leukemia

“…The number of CAR-T clinical trials keeps increasing, aiming to implement alternatives for bad prognosis tumors and expanding their horizons to other types of diseases (HIV, COVID-19, autoimmune diseases, cardiac damage, etc.) [35][36][37] . However, CAR T cells are still at the beginning of their clinical implementation, and a significant fraction (around 50%) of the patients relapse after treatment in a relative short period of time 3,4 .…”

New diagnostic and therapeutic strategies for myocardial infarction via nanomaterials

“…In early 2022, a study reported a revolutionary strategy using liposome nanoparticles encapsulating mRNA translating chimeric antigen receptor (CAR) to realize T cell reprogramming in vivo via CD5 ligand. 119 The synthesized CAR-T cells were able to inhibit myofibroblast proliferation after heart failure but maintained in vivo for less than three days, which induced a transient therapeutic effect after intravenous injection of nanoparticles, thus decreasing the side effect. Such an idea can be expanded on macrophage reprogramming in vivo , which also have the potential to become research hotspots in the future.…”

Signaling cascades in the failing heart and emerging therapeutic strategies

“…Although most of the attention in cardiac cell therapy focuses on the stem cell therapy and in vivo reprogramming, it is worth mentioning that Jonathan A. Epstein’s team proposed a CAR T cell-based anti-fibrosis therapy. 591 , 592 After isolated from human blood, T cells were transduced with a gene coding the CAR, an engineered receptor protein that enable T cells to target a specific protein. The main focus of CAR T cell therapy is its anti-cancer potential.…”