Originally published 2016-06-14.
Can someone else's immune system help fight your cancer? A 2016 laboratory study published in Science suggested that, in part, it can. Researchers in the Netherlands and Norway showed that T cells from healthy donors recognised mutated proteins on melanoma cells that the patients' own T cells had ignored. They then took the donors' recognition receptors and used them to make the patients' own T cells spot the cancer.
The work was a proof of principle in the lab, not a treatment that patients could receive. But it pointed to a new way of personalising immunotherapy, and the ideas behind it have shaped cancer research in the years since. Here is what the scientists did, why it mattered, and what it does and does not mean for people living with cancer.
The study in brief
The paper, "Targeting of cancer neoantigens with donor-derived T cell receptor repertoires", appeared online in Science on 19 May 2016. It was led by Ton Schumacher of the Netherlands Cancer Institute in Amsterdam and Johanna Olweus of the University of Oslo and Oslo University Hospital, working within the K.G. Jebsen Center for Cancer Immunotherapy. The first author was Erlend Strønen.
The team studied tumour samples from three people with melanoma, a serious form of skin cancer. They:
- listed the mutated protein fragments (neoantigens) that the melanoma cells could display;
- checked which of these were recognised by T cells taken from the patients' own tumours;
- exposed T cells from healthy volunteers to the same neoantigens to see which ones the donor cells reacted to;
- transferred the relevant T cell receptors from donor cells into the patients' T cells and tested whether those cells could now recognise the cancer.
Most of the neoantigens went unnoticed by the patients' own tumour-derived T cells. The donor cells, however, responded to a significant number of the ones the patients had missed, and the patients' T cells equipped with donor receptors were able to recognise melanoma cells.
T cells and neoantigens, explained simply
T cells are white blood cells that patrol the body. Each carries a receptor shaped to fit one particular fragment of protein, presented on the surface of other cells by molecules called HLA (also known as MHC). When a T cell's receptor fits a fragment that looks foreign, it can kill the cell or call in the rest of the immune system.
Cancer cells are the body's own cells, which makes them hard to spot. But as tumours grow they accumulate mutations, and some of those mutations produce altered proteins. Fragments of these altered proteins, shown on the cell surface, are called neoantigens. Because healthy cells do not carry them, they are an ideal target: attacking them should spare normal tissue.
The problem is that a patient's immune system often fails to respond. Its repertoire of T cells may simply lack a receptor that fits, or the tumour may suppress the cells that do. The 2016 study tackled the first problem by borrowing receptors from people whose immune systems had never been exposed to the cancer and had not been worn down by it.
What the researchers said
Schumacher summed up the finding by saying that "there is more on the cancer cells that makes them foreign that we can exploit." The approach he described would be to find donor T cells that match a patient's neoantigens, read the receptor they use, and then genetically modify the patient's own T cells to carry it.
Olweus was equally careful about timing. "Our study shows that the principle of outsourcing cancer immunity to a donor is sound," she said in the institutions' announcement, adding that more work was needed before patients could benefit, including faster methods to find which neoantigens donor cells recognise.
Where this fits in cancer immunotherapy
Immunotherapy has changed cancer care over the past decade. Checkpoint inhibitors, which release brakes that tumours put on T cells, have greatly improved outlook for many people with advanced melanoma. Engineered cell therapies form another branch.
The best known is CAR T-cell therapy, in which a patient's T cells are collected, given an artificial receptor that recognises a protein on cancer cells, grown in large numbers and infused back. Early trials in blood cancers produced striking remission rates, widely reported around the time of this study. In August 2017 the US Food and Drug Administration approved the first CAR T product, tisagenlecleucel (Kymriah), for a form of acute lymphoblastic leukaemia in children and young adults. CAR T can cause serious side effects, especially cytokine release syndrome, and it has so far worked far better in blood cancers than in solid tumours.
The 2016 study belongs to a related family: therapies that use natural T cell receptors (TCRs) rather than artificial ones. TCRs can see fragments from inside the cell, including neoantigens, which widens the possible targets. Since then, regulators have approved several therapies along these lines, including tebentafusp for a rare eye melanoma (2022), lifileucel, a therapy using a patient's own tumour-infiltrating T cells, for advanced melanoma (2024), and afamitresgene autoleucel, the first engineered TCR T-cell therapy, for a type of sarcoma (2024). None of these uses donor receptors in the way the 2016 paper explored, but they show the same family of ideas reaching the clinic.
Common misunderstandings
"You can cure cancer with someone else's immune cells." Not from this study. Donor T cells were used in the lab as a source of receptor genes. Whole immune cells from an unrelated person can attack the recipient's body, which is why donor cell transplants need careful matching and carry risks.
"Chemotherapy and radiotherapy are outdated." They remain central, effective treatments for many cancers, often combined with surgery and immunotherapy. Immunotherapy adds options; it has not replaced them.
"Three patients prove it works." Three tumour samples were enough to show a principle. Turning it into a safe treatment requires matching HLA types, confirming that receptors do not react to healthy tissue, manufacturing cells and running clinical trials.
What it means for patients today
For someone with melanoma or another cancer, the honest message is hopeful but measured. Research into neoantigens and engineered T cells has moved quickly since 2016, and clinical trials of personalised approaches are running in many countries. Whether any of them suits a particular person depends on the cancer type, its stage, earlier treatments and overall health.
If you are interested in immunotherapy or a clinical trial, talk to a doctor, ideally your oncologist, who can explain which options are approved, which trials are open and what the risks are.
Sources: ScienceDaily: Fighting cancer with the help of someone else's immune cells (Netherlands Cancer Institute / University of Oslo, May 2016); Strønen et al., Science (2016), doi:10.1126/science.aaf2288; Wikipedia: CAR T cell; Wikipedia: Tumor antigen; first reported by ScienceAlert (Bec Crew, May 2016).
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