Using Autologous Tumor-Infiltrating Lymphocytes to Mediate Tumor Regression: Promising Outcomes in Experimental Research
Experimental research may provide a blue print for the treatment of many types of cancer.
A reported case in an ongoing National Cancer Institute (NCI) clinical trial (ClinicalTrials.gov Identifier: NCT01174121) appears to have extended the known effective range of treatment with antitumor lymphocytes, offering a new, highly personalized immunotherapy approach for metastatic breast cancer.1
Its significance, however, goes far beyond the treatment of breast cancer, according to the report's corresponding author, Steven Rosenberg, MD, PhD, senior investigator and head of the NCI's tumor immunology section.
“This research is experimental right now,” Dr Rosenberg said in a National Institutes of Health press release.2 “But because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”
The reported case involves a 49-year-old woman whose estrogen receptor (ER)-positive breast cancer was refractory to multiple forms of chemotherapy. She was enrolled in an ongoing NCI clinical trial designed to “determine the ability of autologous tumor-infiltrating lymphocytes (TILs) to mediate tumor regression in patients with metastatic epithelial cancers,” according to the report's authors. Study authors concluded, “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 [more than] 22 months.”1
According to the description of the phase 2 trial, the NCI surgery branch is testing an experimental therapy in which white blood cells that have migrated into tumors are taken from the participating patients and grown in large quantities in a laboratory.3 The researchers identified specific neoantigen-reactive T-cell clonotypes and selected ones they expected to be most effective in combating the individual's cancer, then reintroduced those TILs into the original patient.
The goal is to test whether the introduction of the selected TILs can overcome one of the outstanding limitations of this form of therapy.
“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 ovary,” the authors noted.1