Patient's immune cells used to shrink her tumours

In a breakthrough, US scientists have harnessed a female patient's own immune system to shrink her tumours, using a pioneering new technique that offers major advance in fight against cancer.
The method for using immunotherapy to specifically attack tumour cells that have mutations unique to a patient's cancer has been developed by scientists at the National Cancer Institute (NCI).
The researchers demonstrated that the human immune system can mount a response against mutant proteins expressed by cancers that arise in epithelial cells which can line the internal and external surfaces (such as the skin) of the body.
"The method we have developed provides a blueprint for using immunotherapy to specifically attack sporadic or driver mutations, unique to a patient's individual cancer" said Steven A Rosenberg, chief of the Surgery Branch in NCI's Center for Cancer Research.

Research led by Rosenberg and his colleagues had shown that human melanoma tumours often contain mutation-reactive immune cells called tumour-infiltrating lymphocytes, or TILs.
The presence of these cells may help explain the effectiveness of adoptive cell therapy (ACT) and other forms of immunotherapy in the treatment of melanoma.

Rosenberg and his team analysed TILs from a patient with bile duct cancer that had metastasised to the lung and liver and had not been responsive to standard chemotherapy.
The patient, a 43-year-old woman, was enrolled in a National Institutes of Health (NIH) trial of ACT for patients with gastrointestinal cancers.
The researchers first did whole-exome sequencing, in which the protein-coding regions of DNA are analysed to identify mutations that the patient's immune cells might recognise.

Further testing showed that some of the patient's TILs recognised a mutation in a protein called ERBB2-interacting protein (ERBB2IP).
The patient then underwent adoptive cell transfer of 42.4 billion TILs followed by treatment with four doses of the anticancer drug interleukin-2 to enhance T-cell proliferation and function.
Following transfer of the TILs, the patient's metastatic lung and liver tumours stabilised.
When the patient's disease eventually progressed, after about 13 months, she was re-treated with ACT in which 95 per cent of the transferred cells were mutation-reactive T cells, and she experienced tumour regression that was ongoing as of the last follow up (six months after the second T-cell infusion).

These results provide evidence that a T-cell response against a mutant protein can be harnessed to mediate regression of a metastatic epithelial cell cancer.
The study was published in the journal Science.