Science heavy: CAR-T technology upgrades without in vitro programming of T cells

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To date, the application of CAR-T (chimeric antigen receptor T) cell therapy has mainly been in the field of cancer

However, this standard CAR-T cell technology presents problems when targeting human heart failure or other fibrotic diseases

Recently, researchers from the Perelman School of Medicine at the University of Pennsylvania have pioneered an experimental immunotherapy that addresses the specificity of the above-mentioned conventional therapy by transiently reprogramming patients with just a single injection of messenger RNA (mRNA).

In the study, published in the internationally renowned journal Science, the researchers delivered modified mRNAs using T cell-targeting lipid nanoparticles (LNPs) as carriers to generate transient CAR-T cells in vivo to attack cardiac fibroblasts

Photo research results (Source: Science)

In this study, the researchers engineered an mRNA and encapsulated it in CD5-targeted LNP particles (called "targeting antibody/LNP-mRNA carriers" or CD5/LNP-FAPCAR)

CD5-targeted LNPs generate functional mRNA-based FAPCAR-T cells in vitro (Credit: Science)

Next, the researchers assessed whether CD5-targeted LNP-mRNA could also efficiently reprogram T cells in vivo

In another experiment, CD5/LNPs were loaded with mRNA encoding Cre recombinase (CD5/LNP-Cre), which we injected into Ai6 Cre-reporter mice (Rosa26CAG-LSL-ZsGreen)

Forty-eight hours after LNP injection, the results showed a relatively stable FAPCAR+ T cell population (17.

CD5-targeted LNPs generate mRNA-based FAPCAR T cells in vivo (Credit: Science)

The researchers next assessed whether CD5/LNP-FAPCAR treatment could improve cardiac function in injured mice

In addition, LV diastolic function (E/eʹ) returned to uninjured levels

Transient generation of FAPCAR T cells in mice improves cardiac function after injury (Credit: Science)

In conclusion, in this new study, the researchers engineered an mRNA and encapsulated the mRNA in nanoparticle LNPs.

References:

[1] Rurik JG, Tombácz I, Yadegari A, et al.

(Original abridged)