A study test is intended to determine whether individuals receiving immunotherapies are likely to have their cancer relapse or experience severe side effects.
The study, which was published online on September 15 in Clinical Cancer Research, centred on a group of immune system signalling proteins known as antibodies, which identify invading bacteria, viruses, and fungi. These blood proteins are intended to bind to and inactivate specific bacterial and viral proteins, but “autoantibodies” can also respond to the body’s “self” proteins, resulting in autoimmune illness.
The new study, led by researchers at NYU Grossman School of Medicine and its Perlmutter Cancer Center, found that a newly identified panel of autoantibodies, if found in patients’ blood before immunotherapy, has the potential to accurately predict whether a patient’s cancer would recur and if they would experience autoimmune side effects as a result of the treatment itself. The participants in the research had received adjuvant immunotherapy, which aims to prevent cancer from returning after earlier treatment.
Immune cells contain “checkpoint” sensors that switch them off when they receive an adequate signal, protecting normal cells from autoimmune attack. Tumors are recognised as abnormal by the body, but cancer cells hijack checkpoints, particularly programmed death receptor 1 (PD-1), to prevent immune response.
PD-1 inhibitors, a kind of immunotherapy, are effective against various malignancies and are utilised as adjuvant treatment in patients with resected melanoma. Nonetheless, some individuals experience recurrent illness or severe treatment-related adverse effects, according to the study.
The researchers hypothesised that some individuals had greater levels of critical autoantibodies prior to therapy, but not enough to be diagnosed with autoimmune illness. They expected that checkpoint inhibitors would activate this concealed sensitivity, causing increased immune-based adverse effects.
In the current study, the researchers discovered a set of unique autoantibody patterns that might predict immune-related side effects after therapy with two major checkpoint inhibitors, nivolumab and ipilimumab, as well as the combination of the two.
Although their findings support the predictive utility of autoantibody scores when compared to clinical trial data, the researchers believe that more research is needed to validate the value of such a test in the clinic and to better understand the relationship between autoantibodies, recurrence, and toxicity.
“Our findings demonstrate that the new research test has the potential to assist physicians make more precise treatment recommendations by predicting whether a patient will react to a treatment or have adverse effects,” says study first author Paul Johannet, MD. Johannet was a postdoctoral researcher in the laboratory of senior study author Iman Osman, MD, the Rudolf L. Baer Professor of Dermatology at the Ronald O.
Perelman Department of Dermatology and Perlmutter Cancer Center member “With more validation, this composite panel might assist patients better weigh the probability of therapy effectiveness vs severe side effects.”
Blood samples were collected from over 950 individuals who were recruited in one of two Phase 3 randomised controlled trials of adjuvant checkpoint inhibitors in patients with advanced melanoma. Before they got any therapy, these individuals’ tumours were surgically removed and blood samples were obtained. The new test makes use of a microchip with 20,000 proteins connected to it in specified locations. When an antibody detects any of the proteins in a blood sample, those areas illuminate, with the signal becoming stronger as the antibody concentration increases.
Judy Zhong, PhD, and colleagues established a score-based prediction method for each therapy utilised based on the newly found panel of autoantibodies and statistical modelling. According to Zhong, a professor in the Departments of Population Health and Environmental Medicine at NYU Grossman School of Medicine, patients with a high autoantibody recurrence score had a faster illness return than those with a lower score. Similarly, patients with higher pre-treatment autoantibody toxicity levels were considerably more likely than those with lower scores to have severe side effects.
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“The fact that we detected 283 autoantibody signals illustrates that the molecular mechanisms underpinning recurrence and toxicity are complicated and cannot be driven by one or two biomarkers,” adds Osman, who is also the head of the NYU Langone Health Interdisciplinary Melanoma Cooperative Group.
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