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This article is original by Translational Medicine.
Please indicate the source for reprinting.
Author: Daisy Introduction: Chimeric Antigen Receptor (CAR) T cells represent a major breakthrough in cancer treatment, in which the patient’s own T cells are engineered to recognize tumor antigens, resulting in Activation of local cytotoxic immune response
.
However, CAR-T cell therapy is currently limited to the treatment of B-cell cancer, and its effectiveness is affected by the drug resistance of antigen-negative tumor cells, immunosuppression in the tumor microenvironment, the final exhaustion of T cell immune function and frequent severe Toxic hindrance
.
To overcome these problems, a new type of CAR-T cell was developed, which is designed to express enzymes that activate systemically administered small molecule prodrugs in situ at the tumor site
.
Researchers have found that these Synthetase Armed Killer (SEAKER) cells are better than conventional CAR-T cells in killing cancer cells
.
This modular platform can combine targeted cell and small molecule therapies to treat cancer and potentially various other diseases
.
Immunotherapy called Chimeric Antigen Receptor (CAR) T cells uses genetically engineered versions of the patient's own immune cells to fight cancer
.
These treatments provide impetus for cancer treatment, especially for people with certain types of blood cancers
.
Now, scientists at Memorial Sloan Kettering Cancer Center (SKI) have developed new CAR-T cells that can do something that was not possible before: make drugs
.
Standard CAR-T cells are designed in the laboratory to recognize specific markers on cancer cells
.
When these CAR-T cells are returned to the patient, they will proliferate and begin to attack, just like a "living drug
.
"
Although CAR-T is very useful in the treatment of blood cancer, the current CAR-T model still has some limitations
.
One is that CAR-T cells can only kill cancer cells that contain markers they are designed to recognize
.
However, it is not uncommon for cancer cells to stop making such marks and thus "escape" treatment
.
The second problem is that CAR-T cells may become "depleted"-even suppressed by the cancer cells themselves
.
Finally, the existing CAR-T cells are only effective against blood cancers that are easily palpable by CAR-T cells
.
Most of them are powerless to fight against dense solid tumors in the lungs or breasts
.
In order to overcome these obstacles, a team of SKI researchers designed a new type of CAR-T cell as a "micro weapon": it can deliver toxic drug payloads directly to tumors, killing tumors containing cancer markers Cells and nearby cancer cells that do not contain cancer markers
.
More importantly, the engineered cells can produce drugs even when they are exhausted, and the drugs will not be inhibited by cancer
.
David A.
Scheinberg, chairperson of the SKI molecular pharmacology project, head of the Experimental Therapeutics Center, and physician scientist David A.
Scheinberg said: "We call it SEAKER cells.
SEAKER stands for Synthetic Enzyme-Armed KillER cells.
These cells will The ability of immune cells to seek targets is combined with the ability to locally produce effective anti-cancer drugs to achieve a dual effect
.
"This anti-cancer molecule was discovered by Dr.
Derek Tan, Scheinberg's collaborator, the chairman of the SKI Chemical Biology Project, when he was developing antibiotics
.
This molecule, called AMS, is very powerful and cannot be injected directly into the blood of animals
.
But when it is It can effectively and safely kill cancer cells in mice only when it is locally produced at the tumor site
.
Scientists have not tested this technology in humans
.
Details of the SEAKER platform were published in the "Nature Chemical Biology" on December 30.
》 Published an article titled "Engineering CAR-T cells to activate small-molecule drugs in situ"
.
Scientists stated that it is applicable to both cancer and other diseases
.
https:// com/articles/s41589-021-00932-1 Unique drug delivery method The idea of using CAR-T cells to deliver additional therapeutic drugs is not new
.
Several research teams have proven that using them to make immune proteins such as antibodies and cytokines is It is possible
.
But letting CAR-T cells produce small molecule anti-cancer drugs is a more difficult prospect
.
Dr.
Tan said: "Human cells cannot make this compound under normal conditions
.
"In order to find a solution, the team devised a clever method
.
They linked the anti-cancer drug with another chemical substance that "masked" its function
.
Then, they genetically engineered T cells to produce an enzyme that removes the masking molecule from the drug
.
Dr.
Tan added: "Compared with small molecule drugs, human cells are very good at making enzymes, so CAR-T cells can efficiently make enzymes
.
" When the inactive version of the drug, called a prodrug, is injected into the blood , It will circulate in the body
.
The enzymes produced by CAR-T cells act like scissors to release the active part of the prodrug at the tumor site
.
The scientists tested their SEAKER cells on cancer cells grown in petri dishes and mouse models
.
In both cases, SEAKER cells outperform conventional CAR-T cells in killing cancer cells
.
SKI team also showed that their SEAKER cells with several different drugs before and several different lyase work together, so they called the technology "platform"
.
A risky bet paid off.
Scientists emphasized that their research has a "high risk, high reward" nature
.
Dr.
Tan said: "This is one of the wildest ideas I have ever studied
.
It is very exciting to make it work
.
" Thanks to the MSK experimental treatment and the seed funding of the Charity Center, they were able to take risks and eventually Realize this idea
.
Later, the National Institutes of Health (NIH) provided additional funding
.
Dr.
Tan added that the project is a good example of how MSK's pursuit of non-cancer related basic science can produce new discoveries related to cancer
.
Fighting 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, Chief Executive Officer of CoImmune, said: "We have the opportunity to better understand the limitations of CAR-T cells and design new treatments specifically that may address the challenge of eliminating tumor mass and toxicity
.
This exciting The collaboration allows us to evaluate this new treatment and may provide a new treatment option for patients with solid tumors
.
” Dr.
Scheinberg added: “The collaboration with CoImmune is exciting because we need a company to use it for expansion.
Scale and manufacture standardized products
.
"Another attraction of SEAKER technology is that it has more than one possible application
.
Dr.
Scheinberg said: "You can imagine it being used to produce drugs to fight other diseases, such as autoimmune diseases and infections
.
" But for now, MSK researchers and CoImmune will focus on cancer
.
Dr.
Scheinberg speculates that clinical trials for cancer will take approximately two to three years
.
Reference materials: https://medicalxpress.
com/news/2021-12-scientists-retool-car-cells-micropharmacies.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital for treatment
.
Recommendation·Activity [Live Preview] New CRISPR technology combined with high-efficiency electrotransformation technology to help gene editing experience sharing, action knowledge practitioners-Single-cell Scientific Research Creation Camp (Wuhan Station) Popular·Article Basic Research [Science Sub-Journal] Transforming Artificial Lung-Lizard Provides an amazing method! Intestinal flora [Nature] Did you take hypoglycemic drugs ineffective? Because the intestinal microflora is in the process of cancer treatment [PNAS] Chinese medicinal materials thyme and oregano have found anti-cancer compounds for disease diagnosis and treatment [Nature Sub-Journal] This is another step towards changing the US$70 billion global diagnostic industry! Protein biosensors can measure toxic drugs for cardiovascular disease in cancer, arthritis, and organ transplant patients [JAMA Sub-Journal] Are you stressed? Stress increases the risk of cardiovascular disease! Scientific research [Cell Sub-Journal] Why do pain and anxiety speed up the breathing rate? The scientific research "Science" announced the breakthrough of 2021: A problem that has troubled biologists for 50 years was solved by AI and realized the dream of a Nobel Prize winner!
Please indicate the source for reprinting.
Author: Daisy Introduction: Chimeric Antigen Receptor (CAR) T cells represent a major breakthrough in cancer treatment, in which the patient’s own T cells are engineered to recognize tumor antigens, resulting in Activation of local cytotoxic immune response
.
However, CAR-T cell therapy is currently limited to the treatment of B-cell cancer, and its effectiveness is affected by the drug resistance of antigen-negative tumor cells, immunosuppression in the tumor microenvironment, the final exhaustion of T cell immune function and frequent severe Toxic hindrance
.
To overcome these problems, a new type of CAR-T cell was developed, which is designed to express enzymes that activate systemically administered small molecule prodrugs in situ at the tumor site
.
Researchers have found that these Synthetase Armed Killer (SEAKER) cells are better than conventional CAR-T cells in killing cancer cells
.
This modular platform can combine targeted cell and small molecule therapies to treat cancer and potentially various other diseases
.
Immunotherapy called Chimeric Antigen Receptor (CAR) T cells uses genetically engineered versions of the patient's own immune cells to fight cancer
.
These treatments provide impetus for cancer treatment, especially for people with certain types of blood cancers
.
Now, scientists at Memorial Sloan Kettering Cancer Center (SKI) have developed new CAR-T cells that can do something that was not possible before: make drugs
.
Standard CAR-T cells are designed in the laboratory to recognize specific markers on cancer cells
.
When these CAR-T cells are returned to the patient, they will proliferate and begin to attack, just like a "living drug
.
"
Although CAR-T is very useful in the treatment of blood cancer, the current CAR-T model still has some limitations
.
One is that CAR-T cells can only kill cancer cells that contain markers they are designed to recognize
.
However, it is not uncommon for cancer cells to stop making such marks and thus "escape" treatment
.
The second problem is that CAR-T cells may become "depleted"-even suppressed by the cancer cells themselves
.
Finally, the existing CAR-T cells are only effective against blood cancers that are easily palpable by CAR-T cells
.
Most of them are powerless to fight against dense solid tumors in the lungs or breasts
.
In order to overcome these obstacles, a team of SKI researchers designed a new type of CAR-T cell as a "micro weapon": it can deliver toxic drug payloads directly to tumors, killing tumors containing cancer markers Cells and nearby cancer cells that do not contain cancer markers
.
More importantly, the engineered cells can produce drugs even when they are exhausted, and the drugs will not be inhibited by cancer
.
David A.
Scheinberg, chairperson of the SKI molecular pharmacology project, head of the Experimental Therapeutics Center, and physician scientist David A.
Scheinberg said: "We call it SEAKER cells.
SEAKER stands for Synthetic Enzyme-Armed KillER cells.
These cells will The ability of immune cells to seek targets is combined with the ability to locally produce effective anti-cancer drugs to achieve a dual effect
.
"This anti-cancer molecule was discovered by Dr.
Derek Tan, Scheinberg's collaborator, the chairman of the SKI Chemical Biology Project, when he was developing antibiotics
.
This molecule, called AMS, is very powerful and cannot be injected directly into the blood of animals
.
But when it is It can effectively and safely kill cancer cells in mice only when it is locally produced at the tumor site
.
Scientists have not tested this technology in humans
.
Details of the SEAKER platform were published in the "Nature Chemical Biology" on December 30.
》 Published an article titled "Engineering CAR-T cells to activate small-molecule drugs in situ"
.
Scientists stated that it is applicable to both cancer and other diseases
.
https:// com/articles/s41589-021-00932-1 Unique drug delivery method The idea of using CAR-T cells to deliver additional therapeutic drugs is not new
.
Several research teams have proven that using them to make immune proteins such as antibodies and cytokines is It is possible
.
But letting CAR-T cells produce small molecule anti-cancer drugs is a more difficult prospect
.
Dr.
Tan said: "Human cells cannot make this compound under normal conditions
.
"In order to find a solution, the team devised a clever method
.
They linked the anti-cancer drug with another chemical substance that "masked" its function
.
Then, they genetically engineered T cells to produce an enzyme that removes the masking molecule from the drug
.
Dr.
Tan added: "Compared with small molecule drugs, human cells are very good at making enzymes, so CAR-T cells can efficiently make enzymes
.
" When the inactive version of the drug, called a prodrug, is injected into the blood , It will circulate in the body
.
The enzymes produced by CAR-T cells act like scissors to release the active part of the prodrug at the tumor site
.
The scientists tested their SEAKER cells on cancer cells grown in petri dishes and mouse models
.
In both cases, SEAKER cells outperform conventional CAR-T cells in killing cancer cells
.
SKI team also showed that their SEAKER cells with several different drugs before and several different lyase work together, so they called the technology "platform"
.
A risky bet paid off.
Scientists emphasized that their research has a "high risk, high reward" nature
.
Dr.
Tan said: "This is one of the wildest ideas I have ever studied
.
It is very exciting to make it work
.
" Thanks to the MSK experimental treatment and the seed funding of the Charity Center, they were able to take risks and eventually Realize this idea
.
Later, the National Institutes of Health (NIH) provided additional funding
.
Dr.
Tan added that the project is a good example of how MSK's pursuit of non-cancer related basic science can produce new discoveries related to cancer
.
Fighting 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, Chief Executive Officer of CoImmune, said: "We have the opportunity to better understand the limitations of CAR-T cells and design new treatments specifically that may address the challenge of eliminating tumor mass and toxicity
.
This exciting The collaboration allows us to evaluate this new treatment and may provide a new treatment option for patients with solid tumors
.
” Dr.
Scheinberg added: “The collaboration with CoImmune is exciting because we need a company to use it for expansion.
Scale and manufacture standardized products
.
"Another attraction of SEAKER technology is that it has more than one possible application
.
Dr.
Scheinberg said: "You can imagine it being used to produce drugs to fight other diseases, such as autoimmune diseases and infections
.
" But for now, MSK researchers and CoImmune will focus on cancer
.
Dr.
Scheinberg speculates that clinical trials for cancer will take approximately two to three years
.
Reference materials: https://medicalxpress.
com/news/2021-12-scientists-retool-car-cells-micropharmacies.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital for treatment
.
Recommendation·Activity [Live Preview] New CRISPR technology combined with high-efficiency electrotransformation technology to help gene editing experience sharing, action knowledge practitioners-Single-cell Scientific Research Creation Camp (Wuhan Station) Popular·Article Basic Research [Science Sub-Journal] Transforming Artificial Lung-Lizard Provides an amazing method! Intestinal flora [Nature] Did you take hypoglycemic drugs ineffective? Because the intestinal microflora is in the process of cancer treatment [PNAS] Chinese medicinal materials thyme and oregano have found anti-cancer compounds for disease diagnosis and treatment [Nature Sub-Journal] This is another step towards changing the US$70 billion global diagnostic industry! Protein biosensors can measure toxic drugs for cardiovascular disease in cancer, arthritis, and organ transplant patients [JAMA Sub-Journal] Are you stressed? Stress increases the risk of cardiovascular disease! Scientific research [Cell Sub-Journal] Why do pain and anxiety speed up the breathing rate? The scientific research "Science" announced the breakthrough of 2021: A problem that has troubled biologists for 50 years was solved by AI and realized the dream of a Nobel Prize winner!
