A woman treated with a pioneering type of immunotherapy for a solid tumour has been in remission for more than 18 years with no further treatments, experts have revealed.
The therapy involves taking T-cells, a type of white blood cell, from a patient and genetically engineering them to target and kill cancer cells. These modified T-cells are grown in a laboratory and then infused back into the patient.
Known as CAR (chimeric antigen receptor) T-cell therapy, the approach has proved particularly successful in treating certain types of blood cancers. Next-generation forms of the therapy have been approved for such cancers in countries including the US and UK.
However, response rates have been less encouraging in solid tumours, with long-term outcomes unclear.
Now researchers have reported the longest known survival after CAR T-cell therapy for an active cancer, revealing a woman who was treated as a child 18 years ago has remained cancer free. Crucially, the therapy was given for a type of solid tumour called neuroblastoma, a rare cancer of the nerve tissue that develops in children.
Prof Helen Heslop, co-author of the research from Baylor College of Medicine in Houston, Texas, says the trial was one of the earliest to use CAR T-cell therapy for cancer.
“It’s nice to have such long-term follow-up and to see that even if it was a very early CAR T-cell – and there’s been a lot of work to make them better – we were still able to see a clinical remission that’s been sustained for this long, so that she’s grown up and is leading a normal life,” Heslop says.
Writing in the journal Nature Medicine, Heslop and colleagues report how they recruited 19 children to take part in a phase 1 clinical trial of CAR T-cell therapy for neuroblastoma between 2004 and 2009.
Over seven years that followed the therapy, 12 patients died due to relapsed neuroblastoma. Among the seven that survived beyond this point, five were cancer-free when given the CAR T-cell therapy but had previously been treated for neuroblastoma using other approaches and were at high risk of relapse. All five were disease-free at their last follow-up, between 10 and 15 years after the CAR T-cell therapy, although the team note they may already have been cured when the therapy was administered.
The other two surviving patients had cancer that was actively growing or spreading when they received CAR T-cell therapy, but subsequently went into complete remission. One of these patients stopped participating in follow-up sessions eight years after treatment, but the other continued and has remained cancer-free more than 18 years.
“She has never required any other therapy and is likely the longest-surviving patient with cancer who received CAR-T therapy,” the team write. “Encouragingly, she has subsequently had two full-term pregnancies with normal infants.”
The team add the modified T-cells were still detectable in some patients after more than five years. Heslop says that, while it is not known for sure, it could be that CAR T-cells that persist are able to tackle the cancer should it return.
Karin Straathof, the associate professor in tumour immunology at UCL’s Cancer Institute, who was not involved in the new study, says the results are beyond encouraging.
“This is really a solid demonstration that in solid cancers you can achieve complete responses, but also what we want really – and particularly for children’s cancers – long-lasting complete responses,” she says.
But Straathof says further work is needed, adding: “What we now are trying to focus on is understanding why does it work in some patients and why [it] doesn’t work in others, and what we can learn from that to make better designs of these chimeric antigen receptors.”
Encouraging preliminary findings with a new miniCRISPR using a nanoCAS brings hope for previously incurable diseases such as Duchenne muscular dystrophy. The miniCRISPR can reach and edit previously inaccessible tissue including muscle.
Injecting old mice with an RNA molecule called miR-302b seems to reverse some signs of ageing — helping them to live longer, regrow hair and maintain their physical and mental abilities. The treatment works by targeting one of the hallmarks of the ageing process: a stage called cellular senescence, in which cells lose their ability to replicate. Researchers hope the findings could one day lead to the development of anti-ageing drugs, but more work is needed to determine whether they translate to people.
The picture of early-human origins in Africa grows more complex
A sunset view of the Hora site in Malawi. Excavating at the site, researchers found two of the oldest human skeletons in Africa to preserve ancient DNA. The remains have ancestry showing widespread genetic admixture across all of eastern and central Africa. (Jessica Thompson)
For decades, scientists who studied early modern humans believed that our ancestors initially inhabited only small areas of Africa, the savannas of the eastern and southern part of the continent, and then moved north into Asia, Europe and beyond. In this view, early humans bypassed West and Central Africa, especially tropical forests. These areas, the argument went, were populated much later.
But now, a growing group of researchers has cast doubt on this narrative. Working in Senegal, Cameroon, Malawi and elsewhere, they are uncovering evidence that early humans spread across much more of Africa before venturing elsewhere. This work has moved the field beyond the old out-of-Africa narrative and is transforming our understanding of how multiple groups of early modern humans intermingled and spread across the continent, providing a more nuanced picture of our species’ complex origins.
“It’s becoming more and more clear that humans didn't originate in a single population in one region of Africa,” says Eleanor Scerri, an archaeologist at the Max Planck Institute of Geoanthropology in Jena, Germany. “If we really want to understand human evolution, we need to look at all of the African continent.”
Most researchers agree that early modern humans emerged in Africa between 200,000 and 300,000 years ago. About 60,000 years ago, they spread to other parts of the world. Until recently, though, most experts thought these humans populated West and Central Africa, especially the tropical forests there, only within the past 20,000 or so years.
For some researchers, this narrative made little sense. “Humans like to move around a lot,” says University of Pennsylvania geneticist Sarah Tishkoff, who has been working to unravel Africa’s deep genetic lineage for more than two decades. “They had this beautiful continent, they could move all over, go to different niches, with different resources.”
The reason no one found evidence of early human settlement in West and Central Africa, Scerri and others say, is that few people had looked there. For many decades, most researchers tended to focus on low-hanging fruit — areas of the continent where fieldwork was less difficult. Because the climate is dryer and cooler in East and South Africa and the terrain is more open, fossils are easier to find and date. Most of West and Central Africa is hot and humid, so bones and DNA degrade more quickly. In addition, that region can be a challenging place to work, not only because much of it is thickly forested, but also because some areas are enmeshed in long-running and chaotic conflicts.
Some research suggests that cultural bias may also have played a role. “Most research has been spearheaded by people from the global North,” says Yale University paleoanthropologist Jessica Thompson. “And their perspective is, ‘Well, we want to know how people got out of Africa, to where we come from.”
As a result of all these factors, most scientists have focused largely on sites in South and East Africa. This has contributed to the idea that early modern humans primarily inhabited these regions. Frustrated that the academic establishment didn’t take their ideas seriously, a few researchers began trying to uncover evidence that supported their views. Over the past decade or so, they’ve found it.
Last year, a group that included scientists from Senegal, Europe and the United States reported that modern humans had lived at a site on the coast of Senegal 150,000 years ago. Previous estimates put the earliest human habitation in West Africa at 30,000 years ago.
Moreover, the site was in a mangrove forest, rather than the typical grassland or sparse savanna usually associated with early-human habitation. Scerri says her latest research in Senegal, not yet published, may push this date back even further. “It’s clear that there were different people in different places doing different things,” she says. “And they were there for a long time. A lot longer than we realized.”
Another study, from 2022, analyzed DNA from the bones of 34 people who lived across sub-Saharan Africa between 5,000 and 18,000 years ago. Examining such ancient DNA is important because it offers a much clearer window onto the structure of more ancient African populations. The research showed that from 80,000 to 20,000 years ago, populations that had been fairly isolated from one another began to interact across large swaths of the continent. These links spanned thousands of miles, from Ethiopia, through Central African forests and down to South Africa.
“People were clearly moving quite broadly across Africa,” says Thompson, one of the study’s co-authors. “They were not staying in these little isolated populations.”
And a paper published four years ago in Nature examined the remains of two children found at a rock shelter in Cameroon, in the western part of Central Africa. One of the children lived 3,000 years ago, while the other lived 8,000 years ago. The researchers, from Harvard and other institutions, managed to collect DNA from the two — the first ancient human DNA ever sequenced from Central Africa. They detected four separate human lineages between 60,000 and 80,000 years ago, including a previously unknown lineage — what they called a “ghost population” — that probably lived in West Africa. The results provide more support for the idea that humans have been in West Africa for far longer than previously realized and adds to the evidence that humanity’s roots exist across more than one region of Africa.
Experts say it’s important to note that close relatives of modern humans — Neanderthals, Homo erectus and several other species — had already spread beyond Africa to Europe and Asia, in some cases millions of years ago. But these groups contributed relatively small amounts of DNA to the modern human lineage.
Because it can be so difficult to find fossils and retrieve ancient DNA in many parts of Africa, scientists have had to develop innovative approaches to establish early-human habitation. For instance, Thompson and her colleagues studied sediments around Lake Malawi in the northern part of the country. Over thousands of years, the lake shrank and grew, depending on the amount of rainfall. During wetter periods, the number of trees around the lake would expand significantly.
But Thompson found that during a wetter period starting 80,000 years ago (and continuing today), the number of trees did not increase nearly as much as expected. Instead, the scientists found an abundance of charcoal. Thompson says this shows that humans were living in the region, perhaps in fairly large numbers, and were burning wood on a significant scale, either to modify the environment for hunting or to cook or keep warm — or all three.
A key aspect of this new understanding is the Pan-African hypothesis: Scerri and others argue that modern humans probably evolved from the intermingling of different groups from a range of areas of the continent. “There were a number of modern human populations living in different regions of Africa, and we emerged over time from the complex interactions between them,” Scerri says. “Basically, we’re a mix of a mix of a mix of a mix.”
In research published last year, University of California at Davis population geneticist Brenna Henn and her colleagues examined the genomes of almost 300 Africans from across the continent. By analyzing and comparing the genetic data, they were able to construct a model for how humans originated within the continent over the past several hundred thousand years. They found that modern humans descended from at least two distinct populations who lived in different parts of the continent. She and her colleagues are now analyzing genomes from 3,000 people, mostly Africans but also people of African descent who live elsewhere, as well as Indigenous Americans and others.
Scerri has also found evidence to support the Pan-African idea. She has shown that Middle Stone Age culture persisted in West Africa until quite recently, less than about 11,000 years ago. This culture, a particular way of making stone tools, disappeared much earlier in other parts of the continent, 30,000 to 50,000 years ago. This is important, she says, because it is precisely what the Pan-African theory predicts: “In this model, you’d expect that each region would have its own distinctive cultural trajectory, due to periods of isolation. This research shows how this was possible.”
Not everyone is convinced. Richard Klein, a paleoanthropologist at Stanford University who has spent decades studying early modern human origins and migration in Africa, says, “I don’t understand the evolutionary mechanism behind” the pan-African origins theory.
Pontus Skoglund, a population geneticist at the Francis Crick Institute in London who has collaborated with Scerri, says that the Pan-African idea is plausible, but that he isn’t fully persuaded. “To me, it also seems possible that a large portion of present-day people’s ancestry might be found in a single region,” he says. “But we don’t know.” He says there is still “a lot of uncertainty” about who was where and when.
Scerri agrees that more research is needed. But after years of fighting skepticism, she says she feels vindicated that the new perspective has caught on. “Right now, this is such an exciting area to work,” she says. “It’s really an incredible story, one that’s emerging before our eyes.”
About 4.2 million years ago, a microbe emerged with a fairly large genome encoding, that further led through evolution to all the living organisms that we know today as well as those that are now extinct. We do not know how or from where this microbe emerged.
Go to the link below for a fascinating account of the detective work related to the origins of living organisms:
