Immunotherapy method effective against various cancers

Researchers have developed a new method for using immunotherapy to specifically attack tumor cells that have mutations unique to a patient’s cancer.

The National Cancer Institute (NCI), part of the National Institutes of Health (NIH), has demonstrated that the human immune system can mount a response against mutant proteins expressed by cancers that arise in epithelial cells that line the body’s internal and external surfaces, according to a news release. These cells give rise to many types of common cancers, including melanoma.

The research, led by Steven A. Rosenberg, M.D., Ph.D., of the NCI’s Center for Cancer Research, offers evidence that this immune response can be harnessed for therapeutic benefit in patients.

Previous research led by Dr. Rosenberg 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 ACT, a patient’s own TILs are collected, and those with the best anti-tumor activity are lab-grown to produce large populations that are infused into the patient. Prior to the most recent study, it was unclear whether the human immune system could mount an effective response against mutant proteins produced by epithelial cell cancers, which comprise more than 80 percent of all cancers. It was also not known whether such a response could be used to develop personalized immunotherapies for these cancers.

In this study, Dr. Rosenberg and colleagues investigated whether TILs from patients with metastatic gastrointestinal cancers could recognize patient-specific mutations. They analyzed TILs from a 43-year-old female patient with bile-duct cancer that had metastasized to the lung and liver and had not been responsive to standard chemotherapy.

Next: Researchers analyze protein-coding regions of DNA

The researchers first conducted 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, of which about 25 percent were ERBB2IP mutation-reactive T lymphocytes, which are primarily responsible for activating other cells to aid cellular immunity. This was followed by treatment with four doses of interleukin-2 to enhance T-cell proliferation and function.

Following transfer of the TILs, the patient’s metastatic lung and liver tumors stabilized. After about 13 months of the disease’s progression, the patient was re-treated with ACT, in which 95 percent of the transferred cells were mutation-reactive T cells. She experienced tumor regression that was ongoing as of the last follow up (six months after the second T-cell infusion).

According to the study, these results strongly suggest that a T-cell response against a mutant protein can be harnessed to mediate regression of a metastatic epithelial cell cancer.

Cell-transfer immunotherapy represents the best opportunity for patients with metastatic melanoma to achieve a durable complete regression of their cancer and can be effective despite the failure of other treatments.  

“Given that a major hurdle for the success of immunotherapies for gastrointestinal and other cancers is the apparent low frequency of tumor-reactive T cells, the strategies reported here could be used to generate a T-cell adoptive cell therapy for patients with common cancers,” Dr. Rosenberg tells Dermatology Times.

The study was published May 9 issue of the journal Science.

More on Dr. Rosenberg's research:

Gene therapy halts two cases of melanoma

Immune cell replacement shrinks tumors

Melamoma antigens create new therapies

Dr. Rosenberg recognized for cancer research