Scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, have developed a new method for using immunotherapy to specifically attack tumor cells that have mutations unique to a patient’s cancer. The research demonstrates that the human immune system can stand a response against mutant proteins expressed by cancers that arise in epithelial cells, which can line the internal and external surfaces of the body. These cells give rise to many types of common cancers, such as those that develop in the digestive tract, lung, pancreas, bladder, and other areas of the body.
According to the scientists, the research provides evidence that this immune response can be harnessed for therapeutic benefit in patients. The study appeared in the May 2014 journal of Science. The research showed that human melanoma tumors often contain mutation-reactive immune cells called tumor-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. In this study, the researchers set out to determine whether TILs from patients with metastatic gastrointestinal cancers could recognize patient-specific mutations. They analyzed TILs from a patient with bile duct cancer that had metastasized to the lung and liver and had not been responsive to standard chemotherapy.
The researchers first did whole-exome sequencing, in which the protein-coding regions of DNA are analyzed to identify mutations that the patient’s immune cells might recognize. Further testing showed that some of the patient’s TILs recognized a mutation in a protein called ERBB2-interacting protein (ERBB2IP). The patient then underwent adoptive cell transfer of 42.4 billion TILs, approximately 25% of which were ERBB2IP mutation-reactive T lymphocytes, which are primarily responsible for activating other cells to aid cellular immunity, 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 tumors stabilized. When the patient’s disease eventually progressed, after about 13 months, they were the patient was re-treated with ACT in which 95% of the transferred cells were mutation-reactive T cells, and they experienced tumor 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.
Source: National Institutes of Health