iBET researchers would cap CAR T expansion at three days to get fitter cells at lower doses
Researchers at Portugal's iBET argue that capping CAR T cell expansion at three days or less would yield fitter cells at lower doses. Marta Costa's group says the approach also needs faster release assays, since several now take a week or more.
The Scientist · Science desk
Key figures: CAR T manufacturing steps usually take at least 10 days, up to 21 days. A release assay lasting a week takes 7 days. Some 30% of CAR T therapies made each year go unused because the recipient's health deteriorates, per a 2024 analysis.
| Figure | Value | Note | Claim |
|---|---|---|---|
| Manufacturing steps, usual time, at least | 10 days | up to 21 days | 1 |
| Release assay, a week | 7 days | 10 | |
| CAR T therapies made each year that go unused, some | 30% | per a 2024 analysis | 2 |
What happened
- The steps from cell separation through cryopreservation usually take 10 to 21 days.
- A 2024 analysis suggested that some 30% of CAR T therapies made each year go unused because the recipient's health deteriorates during manufacture.
- Most industry efforts to cut vein-to-vein time have focused on process efficiency or decentralized production.
- Today's expansion runs until the culture reaches a target density, often on the order of 10^8 cells, by which point the cells are often fully differentiated and exhausted.
- Costa cites the CliniMACS Prodigy and Lonza's Cocoon, closed systems that run the steps from leukapheresis to final product and are being explored for rapid CAR T production.
Why it matters
- constraint Costa ties short expansion to closed, sensor-equipped automation, so the approach comes with an equipment requirement.
- decision Manufacturers would have to choose between a fixed culture duration and a harvest time set by monitored cell state, which Costa says AI modeling could support.
- exposure Anyone investing in faster ex vivo processes is exposed to in vivo CAR T strategies, which skip ex vivo manufacturing and which Costa says are rapidly gaining momentum.
"Rapid manufacturing changes the manufacturing goal as, instead of maximizing the number of cells produced outside the body, it aims to make fewer but fitter cells, by limiting expansion to three days or less," Marta Costa of iBET told GEN. [5]
The reasoning concerns what a long culture does to the cells. According to Costa, stopping early preserves naive and stem cell-like memory T cells, the populations that multiply and survive much better after infusion, and that can lower the dose a patient needs. [6] She and her colleagues say the resulting product would be as effective as one made from fully differentiated cells. [12] "The evidence increasingly shows that cell quality matters more than cell quantity," Costa said. [15]
That is an argument from researchers, and GEN's write-up does not identify the studies behind it. The thing this doesn't tell you is how much of the unused-therapy share traces to expansion time, since expansion is one step among several in the process. [1]
Costa herself points to a second constraint. "Faster analytics for product release are needed as several assays still take a week or more to assess product safety and potency," she said. [8] A week is seven days, so one assay at the short end of that range runs about 2.3 times as long as the three-day expansion window. [10] If those assays start only after harvest, the benefit of a short culture depends on how fast release testing becomes.
What to watch
- Patient data comparing three-day-expanded products with conventionally expanded ones, at matched and at lower doses.
- Release assays that report in fewer than seven days, since several now take a week or more.
- Clinical results from in vivo CAR T approaches, which would remove the expansion step entirely.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence30
- Adoption
- Insufficient
- Hype gap+25
- Incentives
- Insufficient
- Confidence40
Claim ledger
Ranked by verification strength, evidence, and original report placement.
- [1]
The steps in making a CAR T-cell therapy (separation, enrichment, activation, modification, expansion, harvest and cryopreservation) usually take between 10 and 21 days.
- [2]
An analysis in 2024 suggested that some 30% of CAR T therapies made each year go unused because the intended recipient's health deteriorates while the product is being made.
- [3]
Reducing vein-to-vein time, the time to turn patient-derived material into a therapy and administer it, has become an industry goal, with most efforts focusing on process efficiency or decentralized production.
- [4]
Marta Costa and colleagues at Portugal's iBET say shortening ex vivo expansion, in a 'rapid manufacturing' approach, would yield more effective and more consistent therapies.
- [5]
Costa told GEN: "Rapid manufacturing changes the manufacturing goal as, instead of maximizing the number of cells produced outside the body, it aims to make fewer but fitter cells, by limiting expansion to three days or less."
- [6]
According to Costa, limiting expansion preserves naive and stem cell-like memory T cells, which proliferate and persist much better once infused, and this can ultimately result in lower CAR T cell doses.
- [7]
Costa cites the CliniMACS Prodigy and Lonza's Cocoon as technologies that could facilitate rapid manufacturing; they are being explored for rapid CAR T cell production because they integrate the steps from leukapheresis to final product in one closed system.
- [8]
Costa said: "faster analytics for product release are needed as several assays still take a week or more to assess product safety and potency."
- [9]
Costa said: "Automation is what makes speed safe and allows for reproducibility," and described a closed, standardized, sensor-equipped system as essential to ensure product quality.
- [10]
A release assay lasting a week (7 days) is about 2.3 times as long as the proposed expansion cap of three days.
- [11]
In current manufacturing, expansion runs until the culture reaches a desired density, often on the order of 10^8 cells, and after that period the cells are often fully differentiated and exhausted.
- [12]
Costa and colleagues say limiting expansion would raise the proportion of fitter naive T cells harvested and produce therapies as effective as those made from fully differentiated cells, but at a much lower dose.
- [13]
Costa says most CAR T manufacturing processes follow a fixed recipe regardless of how patients' cells respond, and that AI and data-driven approaches could predict cell growth and differentiation, monitor cell state online, and select the optimal harvest timepoint from the evolving state of the cells rather than a predefined culture duration.
- [14]
Costa says in vivo CAR T cell strategies, which remove ex vivo manufacturing altogether, are rapidly gaining momentum.
- [15]
Costa said: "The evidence increasingly shows that cell quality matters more than cell quantity."
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Sources
1 independent publisher whose own reporting we read for this story.
- genengnews.comContracting Expansion: A Path to Better CAR T-Cell Therapy Production
1 article · October 14, 2026
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