An almost-unprecedented cure for a terminal breast cancer patient using a form of cellular immunotherapy shows that while immuno-oncology is still in its infancy, the potential is enormous.
Judy Perkins had hormone receptor-positive breast cancer that had spread to her liver and other organs and had exhausted all other treatment options, including several rounds of chemotherapy, and none had stopped the disease progressing.
Now, after an infusion of billions of cancer-killing immune cells, and having been given a life expectancy of just a few months, there is no sign of cancer in her body – a “complete, durable regression” in the words of the scientists that developed the therapy.
The new approach – a modified version of a technique known as adoptive cell transfer (ACT) – is being developed by researchers at the National Cancer Institute in the US, and involves sequencing the DNA and RNA of tumours to try to identify mutations that were unique to her specific cancer.
In this case study, they identified 62 mutations, and then tested samples of Perkins’ tumour-infiltrating lymphocytes (TILs) – a form of white blood cell primed to identify and destroy mutated cells – to find those that were particularly active against cells with one or more mutations.
They found a cell line that tackled four mutations, incubated it in the lab to grow a large number of the TILs, and then delivered them via infusion, along with Merck & Co/MSD’s checkpoint inhibitor Keytruda (pembrolizumab) to prevent them being inactivated by factors in the tumour microenvironment.
After the treatment, all trace of Perkins’ cancer disappeared and has not returned more than 22 months later, according to a report in the journal Nature Medicine. There is no published evidence for Keytruda having any effect on HR-positive breast cancer, and the researchers say the short course of the drug is unlikely to have been able to confer such a protracted benefit on its own.
The trial is due to enrol around 330 patients to fully put the technique through its paces, and should be able to generate statistically-validated results in 2023.
Lead investigator Steven Rosenberg said: “Because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”
ACT has been shown to be effective in treating tumours with a high level of mutations such as melanoma, but has been less successful when tested in cancers with a lesser mutation load, such as stomach, oesophageal, ovarian, and breast cancers. The new study suggests that barrier could be overcome.
Rosenberg says investigators have already tested the approach in liver and colorectal cancer, but the “big picture” is that it is not cancer type-specific.
“All cancers have mutations, and that’s what we’re attacking with this immunotherapy”, he said. “It is ironic that the very mutations that cause the cancer may prove to be the best targets to treat the cancer.”
The ACT approach used by the researchers differs a little from chimeric antigen receptor T cell or CAR-T therapy, which have been approved for use in haematological cancers but haven’t shown their mettle yet in solid tumours.
ACT doesn’t involve genetic modification of the T cells to target cancer cell antigens, but it remains to be seen if that has an impact on its safety or efficacy. As with CAR-T, the NCI technique requires the use of high-dose chemotherapy to destroy existing immune cells, which is in itself a risky procedure.