A recent preclinical study using younger and older mice with triple-negative breast cancer (TNBC) sponsored by Boston-based Brigham and Women’s Hospital, the Dana Farber Cancer Institute and Harvard Medical School found that age does, in fact, affect the efficacy of immune checkpoint blockade (ICB) therapy. The young mice experienced a significant reduction in tumor growth and better overall survival rates in response to treatment than those who did not receive the treatment. The aged mice did not see the same benefits from immunotherapy treatment.
The Boston-area researchers injected TNBC cell lines into young mice, aged 8 to 12 weeks, and old mice aged 12 to 15 months. Upon forming palpable tumors, the researchers gave the mice four doses of one of the two ICB drugs—anti-PD-L1 or anti-CTLA-4 antibodies. Additionally, they injected a group with control antibodies. Thereafter they monitored and measured the growth over the tumors over time.
METABRIC Data Base Review
In parallel, the investigators reviewed the METABRIC database, which contains tumor sample data from patients with TNBC. Gene markers that predicted responsiveness to ICB in the young mice were prevalent in younger patients, but not in the older ones. Additionally, the team uncovered signs indicative of the failure of the innate immune system in the tumors of both aged mice and in samples from older patients with TNBC, implying that this study could be relevant to the treatment of people as well.
An Additional Combination Test
The findings in fact established the impetus for the research team to consider a new combination therapy to test. They combined ICB with a STING agonist, a drug that had has immune activation properties and found that tumors in aged mice now responded to ICB and the mice had improved survival.
The team’s work uncovered that age had a profound impact on the response to immunotherapy. The young mice experienced a significant reduction in tumor growth and better overall survival rates in response to the treatment than those who did not receive the treatment. Immunotherapy treatment did not significantly benefit the aged mice compared to those injected with the control.
Sandra McAllister, Ph.D., Brigham’s Hematology Division
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