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Breast cancer. An experimental immunotherapy from the US has cured a woman with an intractable metastatic tumor

June 8, 2018 – Judy’s lymphocytes, a 47-year-old American woman, considered refractory to all traditional treatments, defeated her tumor and her metastases. Judy has been living for

22 months without a trace of the tumor that was killing her, thanks to a new experimental form of immunotherapy that uses tumor-infiltrating lymphocytes, capable of recognizing and thus attacking typical tumor mutations. Preliminary results from this phase 2 study, conducted by the US National Cancer Institute, are published in Nature Medicine.

Immunotherapy continues to make headlines. This time to bounce in the media around the world is a study published in Nature Medicine. And to make this research even more deserving of attention is that it was carried out under the auspices of the National Cancer Institute, part of the

American National Institutes of Health. Having said that, it should be emphasized that these are results obtained on a single patient, which therefore must be taken with all the necessary precautions.

But let’s get to the study. The news is that a new immunotherapy approach has led to complete regression of a breast cancer in the metastatic phase, now refractory to any therapy; in practice, this experimental approach brought back to life a 47-year-old woman, for whom the doctors had decreed the state of off-therapy.

The groundbreaking treatment attempt was led by Steven A. Rosenberg, division of surgery at the NCI Center for Cancer Research.

Tumor-infiltrating lymphocytes hunting for mutations“We have developed a high-performance method – explains Resenberg – to identify tumor mutations, which can be recognized by the immune system. Since this new therapeutic approach is based on the presence of tumor mutations, regardless of the type of tumor, we believe that it can work not only on breast tumors, but also on other tumors ”.

The experimental therapeutic strategy is based on the adoptive transfer of T cells (Adoptive Cell Transfer, ACT), a treatment already used successfully in melanoma, a tumor that has a large number of somatic (acquired) mutations; until now, however, it had not given great results in a number of other cancers (including stomach, esophagus, ovary and breast) that have a low level of mutations.

In this phase 2 trial, currently underway, American researchers have developed a type of ACT that exploits the action of tumor-infiltrating lymphocytes (TILs) to selectively target mutations present in cancer cells. The hypothesis is that this can lead to a reduction in the size of the tumor in these epithelial forms.

How tumor-infiltrating lymphocytes are madeThe TIL ‘production’ technique consists of taking the patient’s blood, isolating the lymphocytes capable of recognizing tumor mutations, making them replicate billions of times, until a large number is obtained, outside the patient’s body.

Subsequently the TILs are reinfused in the patient, who in the meantime has been subjected to a treatment of depletion of the remaining lymphocytes, in order to obtain a more robust immune reaction against the tumor. Subjects in whom this strategy is being tested are also treated with pembrolizumab to protect the re-infused cells from the risk of inactivation.

The experiment on Judy PerkinsThis treatment was tested on Judy Perkins, a Port St. Lucie (Florida) woman with metastatic breast cancer, now refractory to any other treatment. The NCI researchers went to sequence the DNA and RNA of the tumor tissue and of Judy’s normal tissue, to find out which mutations were present only in the tumor;

in this way they were able to identify 62 different mutations in the patient’s cancer cells. At this point, the researchers went to test various TILs isolated from the patient to select those capable of recognizing one or more mutated proteins.

Thus, TILs were isolated able to recognize the mutated version of 4 proteins (SLC3A2, KIAA0368, CADPS2 and CTSB); these are the TILs subjected to expansion and then reinfused in Judy, who was administered pembrolizumab to avoid the possible inactivation of the TILs by the tumor microenvironment.

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