【Nature Sub-Journal】Generate CAR-T cells within 24 hours to benefit more patients!

Introduction: Conventional methods for generating CAR-T cells usually take 9 to 14 days.
Recent studies have reduced the generation time of CAR-T cells to 24 hours.
The new method demonstrates the potential to innovate and improve the production of CAR-T cell therapy, which will benefit more people.
many patients
.
Just 24 hours also offers the possibility to expand where and when these therapies are produced
.
Rapid manufacturing of CAR-T cells may reduce production costs and broaden their applicability
.

A new approach by researchers at Penn Medicine could shorten the time it takes to infuse a patient's immune cells back into the body to find and attack cancer
.
The cell-manufacturing process for this type of immunotherapy pioneered at Penn -- CAR-T cell therapy -- typically takes nine to 14 days
.
In a preclinical study, "Rapid manufacturing of non-activated potent CAR-T cells," published in Nature Biomedical Engineering, a team of researchers at the Perelman School of Medicine at the University of Pennsylvania simplified the process and used the Functional CAR-T cells with enhanced antitumor efficacy were generated in as little as 24 hours
.

results suggest that the time, materials, and labor required to generate CAR-T cells could be substantially reduced, which could be particularly beneficial for patients with rapidly progressive disease and in resource-poor healthcare settings
.
The study was led by Center for Cellular Immunotherapy investigators Michael C.
Milone, MD, Ph.
D.
(Associate Professor of Pathology and Laboratory Medicine) and Saba Ghassemi, Ph.
D.
(Research Assistant Professor of Pathology and Laboratory Medicine)
.

"While traditional manufacturing methods for making CAR-T cells that take days to weeks continue to work for patients with 'liquid' cancers such as leukemia, there is still a need to reduce the time and cost of producing these complex therapies," Milone said
.
Our research, which began in 2018, shortened standard manufacturing methods from 3 days to less than 24 hours, and the manufacturing methods reported in this study demonstrate the potential to innovate and improve the production of CAR-T cell therapies for the benefit of more patients
.
"

CAR-T cell therapy is a type of immunotherapy used to fight cancers in which a patient's own immune cells have been altered
.
T cells are taken from a patient's blood and altered in the laboratory by adding a gene for a receptor called a chimeric antigen receptor, or CAR
.
The CAR-T cells are then infused back into the patient to seek out, bind and destroy cancer cells
.
However, when removed from the body for too long during the engineering process, T cells lose their ability to replicate, which is central to their effectiveness as living drugs
.
So the Penn research team sought to shorten the process without sacrificing T-cell potency
.

In animal models, the researchers learned that the quality, not the quantity, of the CAR-T cell product is an important determinant of its efficacy
.
Their experiments provide evidence that lower numbers of high-quality CAR-T cells generated without extensive expansion in vitro are superior to higher numbers of reduced-quality CAR-T cells that are extensively expanded before being returned to the patient.
T cells
.

Traditional manufacturing methods require stimulating (or "activating") T cells in a way that induces cell replication and population expansion
.
A key to the Penn researchers' fabrication method is a lentiviral vector that delivers the CAR gene to T cells
.
Lentiviral vectors derived from human immunodeficiency virus (HIV) are able to transfer genes into cells like a CAR without this initial "activation" step, but the process is less efficient
.
Using an engineering approach built in part on knowledge of how HIV naturally infects T cells, Penn researchers have developed a method to overcome this need for T cell activation and deliver genes directly to non-activated cells freshly isolated from blood T cells
.
This has the dual benefit of speeding up the entire production process while maintaining the potency of the T cells
.
The patient does not contract HIV through this process
.

The process of engineering T cells is expensive and time-consuming because the treatment must be manufactured for each individual patient
.
The team hopes that shortening the manufacturing time could make the therapy more cost-effective and accessible to more patients
.

"This innovative approach is extraordinary and may be able to help patients who might otherwise not benefit from CAR-T cell therapy, such as those whose cancers are rapidly progressing due to the current time required to generate these therapies," Ghassemi said.

Efficient reprogramming of T cells with CAR in as little as 24 hours in the absence of T cell activation or extensive culture in vitro in a more simplified manufacturing process also provides the opportunity to scale up where and when these therapies are produced.
Possibilities
.
Not only could it increase the production capacity of centralized manufacturing facilities, but if simple and consistent enough, it might be possible to produce these therapies locally near patients, which could equate to solving many of the logistical challenges that hinder this effective therapy, especially in terms of resources in a deprived environment
.
”

The study is a catalyst for more clinical studies to investigate how engineered CAR-T cells, through this shortened approach, work in patients with specific cancers
.

References:

https://medicalxpress.
com/news/2022-03-shorten-car-cell-therapy.
html

Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans
.
For health guidance, please go to a regular hospital for treatment
.