Details of the News That Stage 4 Breast Cancer Was Treated with a New Immunogenetic Therapy

Immune checkpoint inhibitors and adoptive T-cell therapies are particularly effective in skin cancer, smoking-related lung cancer and bladder cancer, where somatic mutations occur frequently. However, their benefit is limited in cancers with a low mutation burden, such as breast, ovarian and gastrointestinal (stomach and intestinal) cancers. In June 2018, Nature published a study that attracted worldwide attention: a newly developed, next-generation immunotherapy approach achieved complete recovery in a patient with metastatic breast cancer that had not responded to other treatments.

In an ongoing phase 2 clinical trial, researchers at the American National Cancer Research Center are investigating whether, by targeting specific mutations , tumor-infiltrating lymphocytes are effective in common epithelial cancers. Promising results were obtained in one patient participating in this clinical trial.

The 49-year-old patient with hormone-positive and HER2-negative metastatic breast cancer had developed resistance to previous chemotherapies.

Treatment Steps:

1. First, a sample of the patient’s tumor underwent DNA and RNA sequencing .
2. In the patient’s tumor, 62 mutations were identified; further analyses then reduced this number to 4.
3. Tumor-infiltrating lymphocytes were isolated from the patient’s tumor and, in the laboratory, enabled to recognize the 4 mutations identified in the patient
4. After being expanded for a period of time, the lymphocytes were returned to the patient.
5. In total, 90 billion lymphocytes were given together with interleukin-2 and the immune checkpoint inhibitor pembrolizumab (Keytruda). Interleukin 2 triggers T-cell proliferation and increases immune system activity. Pembrolizumab prevents the administered T lymphocytes from becoming inactive in the tumor microenvironment .

After treatment, all of the patient’s metastatic tumors disappeared, and no cancer development had been observed for 22 months.

What Does This Study Tell Us?

• An effective cancer immunotherapy method was discovered. Because the method is based on both activating the immune system and modifying it against genetic mutations, it can be called immunogenetic treatment . With this method, cancer-specific mutations can be targeted with immunotherapies. This method is also called adoptive T-cell therapy .
• Mutations in cancer are like cancer’s Achilles heel . Genetic mutations cause cancer to develop. At the same time, these mutations can be used to destroy cancer cells through the immune system.
• This newly developed immunotherapy has also been shown to be effective in other cancer types in the clinical study, such as liver and colorectal (colon and rectal) cancers.
• One of the most important advantages of this method is that it is designed according to the cancer’s genetic structure rather than its type . It can therefore be used in different cancer types.

It is important to emphasize that this newly developed method has been effective in a single patient . This finding needs to be confirmed in clinical trials involving larger numbers of patients.