Science cover report: Injection of mRNA directly generates CAR-T to effectively repair cardiac function

Article source: Medicine Cube Pro

Author: Man

Since the first CAR-T therapy was launched in 2017, 5 CD19 CAR-T and 1 BCMA CAR-T therapy have been approved globally, and the cumulative indications include acute lymphoblastic leukemia, diffuse large B-cell lymphoma, primary Mediastinal B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and multiple myeloma

While CAR-T has made revolutionary progress in the treatment of malignant hematological tumors, scientists and drug developers are also actively exploring other therapeutic potentials of this type of immune cell therapy, including the treatment of solid tumors, as well as other diseases, such as autoimmune diseases, HIV infection,

On January 6, scientists at the Perelman School of Medicine at the University of Pennsylvania published the breakthrough results of CAR-T treatment of heart damage in the form of a cover paper in the journal Science

This achievement not only represents an important breakthrough in the expansion of CAR-T indications, but also a milestone in the field of in vivo CAR-T therapy

Heart failure is caused in part by activated cardiac fibroblasts, which respond to heart damage and inflammation by chronically overproducing fibrous material that hardens the heart muscle and impairs heart function (a process known as cardiac fibrosis).

Most of the CAR-T therapies currently on the market and under development refer to the isolation of T cells from patients, and then the transformation of T cells in vitro to express chimeric antigens that can recognize cancer cell surface antigens (such as CD19, BCMA).

However, using this traditional CAR-T cell therapy to treat human heart failure or other fibrotic diseases presents unique challenges compared to fighting cancer

The LNPs carry mRNA encoding the FAP-targeting CAR, and after injection into mice, the mRNA is delivered to T cells, resulting in transient FAP-targeting CAR expression

To address this issue, in this new study, scientists designed a more temporary, controllable, and simpler procedure for CAR-T cell therapy

CD5-targeted LNPs generate mRNA-based FAP CAR-T cells in vivo (Source: Science)

After the encapsulated mRNA molecules were injected into mice, the mRNA molecules were taken up by T cells and acted as templates for fibroblast targeting receptors, effectively reprogramming the T cells (resulting in FAP-targeting CAR-T cells).

What's more, the scientists found that despite the short-lived existence of the mRNA, injection of this mRNA into mice mimicking heart failure successfully reprogrammed a large number of mouse T cells, resulting in a significant reduction in cardiac fibrosis in the mice.

In vivo generation of transient FAP CAR-T cells improves cardiac function after injury (Source: Science)

It is reported that the researchers are continuing to test this mRNA-based transient CAR-T cell technology, hoping to eventually begin clinical trials

The researchers also say that the ability to transiently express a CAR significantly improves the safety of the treatment

Note: The original text has been deleted

References:

[1] JOEL G.

[2] Vaccine-like mRNA injection can be used to make CAR T cells in the body (Source: Perelman School of Medicine at the University of Pennsylvania)

[3] mRNA shot spawns CAR-T cells in the body to repair heart disease damage (Source: FierceBiotech)

[4] T cells to fix a broken heart (Source: Science)