Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer
From “Nature: Medicine”
https://www.nature.com/articles/s41591-018-0040-8
Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations—such as melanoma, smoking-induced lung cancers and bladder cancer—with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1,2,3,4,5,6,7. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers8,9,10,11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins—SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.
Analysis:
This is a patient with metastatic breast cancer who did not respond to chemotherapy (“chemorefractory”). This is a disease that is generally considered treatable but not curable, and patients with chemorefractory disease are often considered terminally ill.
This patient was treated with immune cells (tumor-infiltrating lymphocytes) that were specifically “trained” against mutated proteins only found in the cancer cells (SLC3A2, etc). The researchers tossed in some other “helper” meds, including the immune cell controller interleukin 2 and a “Checkpoint Blockade” (another facet that essentially takes the gloves off of parts of the immune system) medication.
The result was a “complete, durable regression” (i.e., “cure”) which has held for greater than 22 months. They won’t call it a true “cure” until 5 years out. We’re so used to cancers like this being incurable that the term complete regression seems more palatable to oncologists. Hopefully in the future, the language will change as we see real “cures” for this kind of disease.
This is “only” one patient, but if it’s reproducible, this will add another large chunk of ammunition in the war against cancer.
yr obt svt,
Steve
