A new approach to immunotherapy developed by researchers at the National Cancer Institute (NCI) has resulted in a positive response in a once unresponsive breast cancer patient.
Talking about this new immunotherapy, Dr Rosenburg, lead on the clinical trial and chief of the Surgery Branch at NCI’s Center for Cancer Research (CCR), said: “We’ve developed a high-throughput method to identify mutations present in a cancer that are recognised by the immune system.
“This research is experimental right now. But 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.”
What was the new approach?
The immunotherapy approach is a modified form of adoptive cell transfer (ACT). ACT has been effective in treating melanoma, which has high levels of somatic, or acquired, mutations.
However, this has been less effective with some epithelial cancers or cancers that start in the lining of organs that have lower levels of mutations, such as stomach, oesophageal, ovarian, and breast cancers.
An ongoing phase II clinical trial is seeing investigators develop a form of ACT that uses tumour-infiltrating lymphocytes (TILs) that specifically target tumour cell mutations to see if they can shrink tumours in patients with these common epithelial cancers.
In order to create a stronger immune response against the tumour, selected TILs are grown to large numbers in the laboratory and infused back into the patient.
A positive response
After receiving multiple treatments, one patient’s breast cancer continued to develop and there was nothing else that could be done.
She came to the trial where researchers sequenced DNA and RNA from one of her tumours, as well as normal tissue to see which mutations were unique to her cancer and identified 62 different mutations in her tumour cells.
Researchers tested different TILs from the patient to find those that recognised one or more of these mutated proteins.
Four of the mutant proteins were recognised by TILs and they were then expanded and infused back into the patient.
She was also given the checkpoint inhibitor pembrolizumab to prevent the possible inactivation of the infused T-cells by factors in the tumour microenvironment. Following the treatment, all of this patient’s cancer disappeared and over 22 months later has not returned.
“The power of immunotherapy”
Tom Misteli, PhD, director of CCR at NCI, added: “This is an illustrative case report that highlights, once again, the power of immunotherapy.
“If confirmed in a larger study, it promises to further extend the reach of this T-cell therapy to a broader spectrum of cancers.”
The findings were published in Nature Medicine.
Source: National Cancer Institute