Sub-Journal of "Nature": Miniature Drug Factory——CAR-T Cells

Standard CAR-T cells are designed in the laboratory to identify specific markers on cancer cells

Although CAR-T is very useful in the treatment of blood cancer, the current CAR-T model still has some limitations

The second problem is that CAR-T cells may be "depleted"-even suppressed by the cancer cells themselves

In order to overcome these obstacles, a group of SKI's brand-new CAR T cells function as a "micro weapon": it can deliver toxic drugs directly to the tumor, killing tumor cells containing cancer markers and cancer cells that are not nearby

"We call them SEAKER cells," said medical scientist David A.

This anti-cancer molecule was discovered by Derek Tan, chairman of the SKI Chemical Biology Project, when he was developing antibiotics, and he was Dr.

The details of the SEAKER platform have been published in the journal Nature Chemical Biology on December 30, 2021

Unique drug delivery method

The idea of ​​using CAR-T cells to provide additional therapeutic drugs is not entirely new

Dr.

In order to find a workaround, the team came up with a clever way

"Compared with small molecule drugs, human cells are very good at making enzymes, so CAR-T cells can efficiently make enzymes," Dr.

When the inactive version of the drug, called the prodrug, is injected into the blood, it circulates throughout the body

The scientists tested their SEAKER cells on cancer cells grown in petri dishes and mouse models

SKI team also showed that different cells and their SEAKER several prodrugs and several different lyase work, so they will be called the technology "platform"

A risky bet that pays off

The scientists emphasized that their research has a "high risk and high reward" nature

"This is one of the craziest ideas I have ever studied," Tan said

Thanks to seed funding and charity from the MSK Experimental Treatment Center, they were able to take the risk and finally realized this idea
.
Later, the National Institutes of Health (NIH) provided additional funding
.

Tan added that this project is a good example of how basic scientific research at MSK that has nothing to do with cancer can lead to new discoveries related to cancer
.

"Looking for" cancer and other diseases

Now that scientists have shown that their SEAKER cells work in mice, there is a lot of interest in this method
.
In fact, a company called CoImmune has obtained a license for this technology from MSK to develop CAR-T cell technology for human trials
.

Dr.
Charles Nicolette, CEO of CoImmune, said: "We have the opportunity to better understand the limitations of CAR-T cells and design new treatments specifically to solve the challenge of eliminating tumor mass and toxicity
.
This exciting The collaboration will allow us to evaluate this new approach, which may provide a new treatment option for patients with solid tumors
.
"

"The collaboration with CoImmune is exciting because we need a company to scale up and produce standardized products," Dr.
Scheinberg added
.

Another attraction of SEAKER technology is that it has multiple possible applications
.

"You can imagine it being used to produce drugs for other diseases, such as autoimmune diseases and infections," said Dr.
Scheinberg
.

But for now, the focus of MSK researchers and CoImmune will be cancer
.
Dr.
Schinberg speculates that clinical trials for cancer will take about two to three years
.

Thomas J.
Gardner, J.
Peter Lee, Christopher M.
Bourne, Dinali Wijewarnasuriya, Nihar Kinarivala, Keifer G.
Kurtz, Broderick C.
Corless, Megan M.
Dacek, Aaron Y.
Chang, George Mo, Kha M.
Nguyen, Renier J.
Brentjens, Derek S.
Tan, David A.
Scheinberg.
Engineering CAR-T cells to activate small-molecule drugs in situ .
Nature Chemical Biology , 2021; DOI: 10.
1038/s41589-021-00932-1