🧬 Scientists Find the "Off Switch" That Exhausts CAR T Cells — and Show How to Flip It
CAR T-cell therapy is one of the most powerful tools in modern oncology: take a patient's own immune cells, genetically reprogram them to hunt cancer, and put them back. It works wonders against some blood cancers. But against solid tumors — the majority of cancer cases — CAR T cells burn out too fast. Now, an international team has pinpointed exactly why.
Researchers at Columbia University and University Hospital Tübingen, led by CAR T pioneer Prof. Michel Sadelain and Prof. Judith Feucht, screened roughly 400 transcription factors — proteins that act as master switches for gene activity inside cells. One protein stood out dramatically: NFIL3. It turned out to be a primary driver of T-cell exhaustion, the process that gradually strips engineered immune cells of their cancer-killing power.
Using CRISPR/Cas9 gene editing, the team snipped out the gene responsible for NFIL3. The result? The edited CAR T cells stayed active significantly longer, multiplied more efficiently, and maintained a sustained anti-tumor assault. In mouse models, NFIL3-disabled cells delivered stronger tumor control and extended survival compared to standard CAR T cells.
Key findings:
— NFIL3 was identified as the dominant transcription factor driving CAR T-cell exhaustion out of ~400 candidates screened
— CRISPR deletion of NFIL3 kept CAR T cells functional and proliferating for much longer periods
— NFIL3-knockout CAR T cells showed superior tumor control across multiple animal models, including solid tumors
— The approach targets the biology of exhaustion itself rather than the tumor type, potentially helping across many cancers
"Switching off NFIL3 could be a decisive step toward significantly improving the long-term potency of CAR T cells," said Prof. Feucht. "We expect this to open up new possibilities in the treatment of cancer patients."
Why it matters: CAR T therapy has been a revolution in blood cancers but has largely failed against solid tumors — breast, lung, pancreatic, brain — because the engineered cells simply don't last. This discovery offers a concrete, druggable target to make CAR T durable enough for the cancers that kill the most people. It's not a new therapy — it's a way to make the existing one finally work where it's needed most.
📄 Original paper (Cancer Discovery): https://doi.org/10.1158/2159-8290.CD-25-1524
📖 Readable summary: https://www.sciencedaily.com/releases/2026/06/260602021641.htm
#CARTcell #CancerResearch #CRISPR #Immunotherapy #Oncology
CAR T-cell therapy is one of the most powerful tools in modern oncology: take a patient's own immune cells, genetically reprogram them to hunt cancer, and put them back. It works wonders against some blood cancers. But against solid tumors — the majority of cancer cases — CAR T cells burn out too fast. Now, an international team has pinpointed exactly why.
Researchers at Columbia University and University Hospital Tübingen, led by CAR T pioneer Prof. Michel Sadelain and Prof. Judith Feucht, screened roughly 400 transcription factors — proteins that act as master switches for gene activity inside cells. One protein stood out dramatically: NFIL3. It turned out to be a primary driver of T-cell exhaustion, the process that gradually strips engineered immune cells of their cancer-killing power.
Using CRISPR/Cas9 gene editing, the team snipped out the gene responsible for NFIL3. The result? The edited CAR T cells stayed active significantly longer, multiplied more efficiently, and maintained a sustained anti-tumor assault. In mouse models, NFIL3-disabled cells delivered stronger tumor control and extended survival compared to standard CAR T cells.
Key findings:
— NFIL3 was identified as the dominant transcription factor driving CAR T-cell exhaustion out of ~400 candidates screened
— CRISPR deletion of NFIL3 kept CAR T cells functional and proliferating for much longer periods
— NFIL3-knockout CAR T cells showed superior tumor control across multiple animal models, including solid tumors
— The approach targets the biology of exhaustion itself rather than the tumor type, potentially helping across many cancers
"Switching off NFIL3 could be a decisive step toward significantly improving the long-term potency of CAR T cells," said Prof. Feucht. "We expect this to open up new possibilities in the treatment of cancer patients."
Why it matters: CAR T therapy has been a revolution in blood cancers but has largely failed against solid tumors — breast, lung, pancreatic, brain — because the engineered cells simply don't last. This discovery offers a concrete, druggable target to make CAR T durable enough for the cancers that kill the most people. It's not a new therapy — it's a way to make the existing one finally work where it's needed most.
📄 Original paper (Cancer Discovery): https://doi.org/10.1158/2159-8290.CD-25-1524
📖 Readable summary: https://www.sciencedaily.com/releases/2026/06/260602021641.htm
#CARTcell #CancerResearch #CRISPR #Immunotherapy #Oncology
ScienceDaily
A single protein may be holding back CAR T cancer therapy
A newly identified protein may be one of the biggest obstacles holding CAR T-cell therapy back. Researchers found that NFIL3 causes these engineered immune cells to become exhausted and lose their cancer-fighting power over time. When NFIL3 was disabled,…
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🧬 An AI Just Made a Biological Discovery
Not summarized a paper.
Not predicted a protein structure.
Found something in nature that scientists apparently hadn’t noticed before.
Researchers gave Claude AI agents a relatively broad task: search enormous DNA databases for unusual reverse transcriptases — enzymes that copy RNA into DNA.
Then they mostly stepped aside.
About 950 AI agents spent 21 hours analyzing more than 200,000 enzymes, narrowing them to 3,500 candidate systems and eventually 20 especially interesting ones.
One agent noticed something strange.
Next to a reverse transcriptase gene in a bacteriophage — a virus that infects bacteria — it found a long, organized array of repeating DNA sequences.
The pattern looked oddly familiar.
It resembled the repeat architecture of CRISPR.
Claude investigated the sequence, measured the repeats, compared them with known systems and searched the scientific literature. It concluded that the combination appeared to represent a previously uncharacterized biological system.
Human scientists then took over in the laboratory.
Their initial experiments supported a key prediction: the mysterious DNA array is actually expressed into multiple short RNA molecules.
The researchers named the system ART — array-associated reverse transcriptases.
And this is where the story gets interesting.
CRISPR also contains arrays that generate short RNAs, which ultimately help make the system programmable. Several other recently discovered molecular systems with similar combinations of features can cut, copy or insert genetic material.
But an important warning: nobody yet knows what ART actually does.
This is an early preprint, not a peer-reviewed discovery, and there is currently no evidence that ART is a new gene-editing system. Experiments are still underway to determine its biological function.
The bigger story may therefore be Claude itself.
For decades, biological discovery depended partly on humans noticing something strange hidden inside enormous datasets.
Now we may have machines capable of doing the noticing.
What happens when thousands — or millions — of AI scientists start searching nature simultaneously?
#AI #Biology #CRISPR #Genetics #Biotechnology #Claude #Science
https://www.anthropic.com/news/claude-discovers-novel-enzyme-system
Not summarized a paper.
Not predicted a protein structure.
Found something in nature that scientists apparently hadn’t noticed before.
Researchers gave Claude AI agents a relatively broad task: search enormous DNA databases for unusual reverse transcriptases — enzymes that copy RNA into DNA.
Then they mostly stepped aside.
About 950 AI agents spent 21 hours analyzing more than 200,000 enzymes, narrowing them to 3,500 candidate systems and eventually 20 especially interesting ones.
One agent noticed something strange.
Next to a reverse transcriptase gene in a bacteriophage — a virus that infects bacteria — it found a long, organized array of repeating DNA sequences.
The pattern looked oddly familiar.
It resembled the repeat architecture of CRISPR.
Claude investigated the sequence, measured the repeats, compared them with known systems and searched the scientific literature. It concluded that the combination appeared to represent a previously uncharacterized biological system.
Human scientists then took over in the laboratory.
Their initial experiments supported a key prediction: the mysterious DNA array is actually expressed into multiple short RNA molecules.
The researchers named the system ART — array-associated reverse transcriptases.
And this is where the story gets interesting.
CRISPR also contains arrays that generate short RNAs, which ultimately help make the system programmable. Several other recently discovered molecular systems with similar combinations of features can cut, copy or insert genetic material.
But an important warning: nobody yet knows what ART actually does.
This is an early preprint, not a peer-reviewed discovery, and there is currently no evidence that ART is a new gene-editing system. Experiments are still underway to determine its biological function.
The bigger story may therefore be Claude itself.
For decades, biological discovery depended partly on humans noticing something strange hidden inside enormous datasets.
Now we may have machines capable of doing the noticing.
What happens when thousands — or millions — of AI scientists start searching nature simultaneously?
#AI #Biology #CRISPR #Genetics #Biotechnology #Claude #Science
https://www.anthropic.com/news/claude-discovers-novel-enzyme-system
Anthropic
Claude discovers a novel enzyme system with CRISPR-like repeats
In early results from our new life sciences research lab, Claude agents found an enzyme system whose function is still unknown.
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