NIH Study Reveals New Cancer Immunotherapy Method

Scientists at the National Cancer Institute (NCI) have developed a new method for using immunotherapy to specifically attack tumor cells that have mutations unique to a patient’s cancer. The research showed that human melanoma tumors often contain mutation-reactive immune cells called tumor-infiltrating lymphocytes (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, which appeared in the May 2014 issue of Science, 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 used whole-exome sequencing, in which the protein-coding regions of DNA are analyzed to identify mutations that the patient’s immune cells might recognize. They found 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 mutationreactive T lymphocytes, 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 progressed, they were retreated with ACT in which 95% of the transferred cells were mutation-reactive T cells, and experienced tumor regression that was ongoing six months after the second T-cell infusion. These results suggest that a T-cell response against a mutant protein can be harnessed to mediate regression of a metastatic epithelial cell cancer.