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Breast cancer unresponsive to other treatments: new approach to immunotherapy leads to complete response


A novel approach to immunotherapy developed by researchers at the National Cancer Institute ( NCI ) has led to the complete regression of breast cancer in a patient who was unresponsive to all other treatments. This patient received the treatment in a clinical trial led by Steven A. Rosenberg, Surgery Branch at NCI’s Center for Cancer Research ( CCR ), and the findings were published in Nature Medicine.

The new immunotherapy approach is a modified form of adoptive cell transfer ( ACT ). ACT has been effective in treating melanoma, which has high levels of somatic, or acquired, mutations.
However, it has been less effective with some common epithelial cancers, or cancers that start in the lining of organs, that have lower levels of mutations, such as stomach, esophageal, ovarian, and breast cancers.

In an ongoing phase 2 clinical trial, the investigators are developing a form of ACT that uses tumor-infiltrating lymphocytes ( TILs ) that specifically target tumor cell mutations to see if they can shrink tumors in patients with these common epithelial cancers.
As with other forms of ACT, the selected TILs are grown to large numbers in the laboratory and are then infused back into the patient ( who has in the meantime undergone treatment to deplete remaining lymphocytes ) to create a stronger immune response against the tumor.

A patient with metastatic breast cancer came to the trial after receiving multiple treatments, including several chemotherapy and hormonal treatments, that had not stopped her cancer from progressing.
To treat her, the researchers sequenced DNA and RNA from one of her tumors, as well as normal tissue to see which mutations were unique to her cancer, and identified 62 different mutations in her tumor cells.

The researchers then tested different TILs from the patient to find those that recognized one or more of these mutated proteins.
TILs recognized four of the mutant proteins, and the TILs then were expanded and infused back into the patient.
She was also given the checkpoint inhibitor Pembrolizumab ( Keytruda ) to prevent the possible inactivation of the infused T cells by factors in the tumor microenvironment.
After the treatment, all of this patient’s cancer disappeared and has not returned more than 22 months later.

Researchers have seen similar results using mutation-targeted TIL treatment for patients in the same trial with other epithelial cancers, including liver cancer and colorectal cancer. ( Xagena )
Source: National Institutes of Health, 2018

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