The world this week

News in focus
EYE OF SCIENCE/SPL

Engineered immune cells (yellow) have revolutionized treatment for some tumours (pink) and could help to treat autoimmune diseases.

WORLD-FIRST THERAPY USING

DONOR CELLS SENDS AUTOIMMUNE
DISEASES INTO REMISSION
The treatment’s success in three people raises hopes
for mass production of cutting-edge CAR-T therapies.
By Smriti Mallapaty

T
which affects connective tissue and can result cells release autoantibodies that attack the
in skin stiffening and organ damage. He says body’s own tissue. But the therapy typically
he severe autoimmune conditions of that three days after receiving the therapy, he relies on a person’s own immune cells, and this
one woman and two men have gone felt his skin loosen and he could start moving personalization makes it expensive and time
into remission after being treated with his fingers and opening his mouth again. Two consuming.
bioengineered and CRISPR-­modified weeks later, he returned to his office job. “I Researchers have therefore started creating
immune cells1. The three individuals feel very good,” he says, more than a year after CAR-T therapies from donated immune cells.
from China are the first people with autoim- receiving the treatment. If successful, the approach would allow phar-
mune disorders to be treated with engineered Engineered immune cells, called chimeric maceutical companies to scale up manufactur-
immune cells created from donor cells, rather antigen receptor (CAR) T cells, have shown ing, potentially slashing costs and production
than ones collected from their own bodies. great promise in treating blood cancers, half times. Instead of making one treatment for one
This advance is the first step towards mass a dozen products having been approved in the person, therapies for more than 100 people
production of such therapies. United States. They also show potential for could be made from one donor’s cells, says Lin
One of the recipients, Mr Gong, a 57-year-old treating autoimmune conditions such as lupus Xin, an immunologist at Tsinghua University in
man from Shanghai, has systemic sclerosis, and multiple sclerosis, in which rogue immune Beijing. Donor-derived CAR T cells have been

Nature | Vol 634 | 17 October 2024 | 519

News in focus
used to treat people with cancers, but with remission, and maintained that status at her But the researchers are still trying to deter-
limited success so far2. six-month follow-up. Baker says that although mine whether the host’s body rejects the graft
The trial, led by Xu Huji, a rheumatologist the woman showed clear clinical improve- over time.
at Naval Medical University in Shanghai, is ments, he would be more cautious about One key safety concern observed in some
the first to report results for autoimmune calling it complete remission, given the short people who have received CAR-T-cell therapy
diseases. More than six months after receiv- assessment time. The woman’s autoantibodies for cancer is the emergence of new tumours,
ing the treatment, the recipients’ conditions had dropped to undetectable levels, and her although researchers are still investigating
remained in remission. Another two dozen muscle strength and mobility had improved whether they are linked to the therapy. Baker
individuals have received the donor-derived drastically. says it’s too early to know whether people with
treatment and a slightly modified product, The two men also saw significant improve- autoimmune conditions who are treated with
says Xu. The results have been largely positive, ments in their symptoms — including the heal- donor-derived CAR T cells will face this risk.
he says. ing of scar-tissue formation — and declines in “Only time will tell.”
“The clinical outcomes are phenomenal,” autoantibody levels. The big question now, Baker says, is whether
says Lin, who is leading a separate trial using None of the individuals experienced an the same approach will work in more people,
donor-derived CAR T cells to treat lupus. extreme inflammatory reaction known as and how durable the effects will be. “Will these
The success and safety of the therapy look cytokine-release syndrome, which has been patients stay symptom-free for years?”
promising, but still need to be demonstrated observed in some people with cancer who
in many more people before researchers can have received CAR-T therapy, and there was 1. Wang, X. et al. Cell 187, 4890–4904 (2024).
2. Chiesa, R. et al. N. Engl. J. Med. 389, 899–910 (2023).
draw conclusions about its broad application, no evidence of the graft attacking the host. 3. Müller, F. et al. N. Engl. J. Med. 390, 687–700 (2024).
says Christina Bergmann, a rheumatologist at
the University Hospital Erlangen in Germany.
But if it does succeed in more people over

BACTERIA IMPLANTED IN
a longer time frame, it “could prove paradigm
shifting”, says Daniel Baker, an immunologist

FUNGI HINTS AT ORIGINS

at the University of Pennsylvania in Philadel-
phia. More than 80 autoimmune diseases are

OF COMPLEX LIFE
linked to malfunctioning immune cells.

Healthy donor
CAR-T-cell therapy typically involves extract-
ing immune cells known as T cells from the per- Symbiotic system suggests how mitochondria and
son being treated. The cells are embellished
with CAR proteins that target B cells and are chloroplasts might have emerged a billion years ago.
then re-infused into the person’s body.
By Ewen Callaway

S
The process for creating CAR T cells from up residence inside an ancestor of eukaryotic
donated immune cells is similar. Xu and his cells. Chloroplasts emerged when an ances-
colleagues extracted T cells from a 21-year-old cientists wielding a minute hollow tor of plants swallowed a photosynthetic
woman and studded them with CARs that rec- needle — and a bike pump — have man- microorganism.
ognize CD19, a receptor found on the surface aged to implant bacteria into a larger Determining the factors that formed and
of B cells. They used the CRISPR–Cas9 gene-ed- cell, creating a relationship that might sustained these couplings is difficult because
iting tool to knock out five genes in the T cells, have helped to spark the evolution of they occurred so long ago. To get around this
to prevent both the grafted cells from attack- complex life. problem, a team led by microbiologist Julia
ing the host’s body and the host’s immune The feat — described in Nature on 2 October Vorholt, at the Swiss Federal Institute of Tech-
system from attacking the donor cells. (G. H. Giger et al. Nature https://doi.org/g6z4pp; nology in Zurich (ETH Zurich), has spent the
The first person to receive the treatment, 2024) — could help researchers to understand past few years engineering endosymbioses
in May 2023, was a 42-year-old woman with the origins of pairings like those that gave rise in the laboratory. Their approach uses a
a type of autoimmune myopathy, which tar- to specialized organelles, the most prominent 500–1,000-nanometre-wide needle to punc-
gets skeletal muscle tissue, resulting in weak- being mitochondria and chloroplasts, which ture host cells and then deliver bacterial cells
ness and fatigue. Mr Gong, and another man emerged more than one billion years ago. one at a time.
aged 45, had an aggressive form of sclerosis.
Sparking symbiosis
They started their treatments in June and “There are ways for
August 2023. Even with this technical wizardry, initial pair-
Once injected into the hosts, the CAR T cells
these two partners to ings tended to fail; for instance, because the
got to work. They multiplied and then targeted make a better, easier would-be symbiont divided too fast and killed
and destroyed all the B cells — including path- living with each other.” its host (C. G. Gäbelein et al. ACS Synth. Biol. 11,
ogenic cells linked to the autoimmune condi- 3388–3396; 2022). The team’s luck changed
tions. The bioengineered T cells survived for when the researchers recreated a natural sym-
weeks in the recipients before largely vanish- Endosymbiotic relationships — in which biosis that occurs between some strains of a
ing. Eventually, new healthy B cells returned, a microbial partner lives harmoniously in fungal plant pathogen, Rhizopus microsporus,
but no pathogenic ones did. A similar response the cells of another organism — are found in and the bacterium Mycetohabitans rhizoxi-
has been observed in people with autoimmune numerous life forms, including insects and nica, which produces a toxin that protects the
conditions who received CAR T cells derived fungi. fungus from predation.
from their own cells3. Scientists think that mitochondria, the orga- Yet delivering bacterial cells into the fungi,
Two months after the treatment, the nelles that are responsible for cells’ energy which have thick cell walls that maintain
researchers say the woman achieved complete production, evolved when a bacterium took a high internal pressure, was a challenge.

520 | Nature | Vol 634 | 17 October 2024