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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Friday, February 25, 2022
Steven A. Rosenberg, MD, PhD, of the National Cancer Institute, Bethesda, Maryland, and colleagues conducted a phase II study investigating the immunogenicity of somatic mutations in breast cancer and evaluated the therapeutic efficacy of mutation-reactive tumor-infiltrating lymphocytes (TILs) in patients with metastatic breast cancer. Published in the Journal of Clinical Oncology, these results suggest that this type of personalized immunotherapy may be used to treat patients who have exhausted all other treatment options.
“It’s fascinating that the Achilles’ heel of these cancers can potentially be the very gene mutations that caused the cancer,” said Dr. Rosenberg in a National Institutes of Health press release. “We’re using a patient’s own lymphocytes as a drug to treat the cancer by targeting the unique mutations in that cancer. This is a highly personalized treatment.”
This trial enrolled a total of 42 patients with metastatic breast cancer who were refractory to previous treatment. Participants underwent surgical resection of metastatic regions, isolation of TIL cultures, immunologic screening, and identification of tumor mutations. Individuals who were clinically eligible were enrolled in an ongoing phase II pilot trial of adoptive cell transfer of selected neoantigen-reactive TILs, along with pembrolizumab.
From the resected lesions of all 42 patients, TILs were isolated and grown in culture; a median number of 112 nonsynonymous mutations were identified per patient. Notably, the majority (67%) of participants harbored TILs that recognized immunogenic somatic mutations, with a median of 3 neoantigens per patient; 13 individuals appeared to show reactivity that was appropriate for adoptive transfer.
The most common genetic aberrations were found in TP53 (37%), KMT2D (44%), BCL2 (41%), and CDKN2A (37%). Of note, 25 of these individuals had a total of 28 mutations in the TP53 gene; 5 patients had copy number alterations without mutations. A total of eight patients were identified as clinically eligible for treatment, six of whom underwent adoptive cell transfer of enriched neoantigen-specific TILs, in combination with pembrolizumab. Objective tumor regression was observed in three patients, including one complete and two partial responses.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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