The ASCO Foundation
A new study reveals that autoantibodies that occur naturally in our body can increase or hinder the effectiveness of cancer immunotherapy up to 10 times, offering new perspectives on why these treatments only work for some patients.
In a recent study, a team of Yale School of Medicine (YSM) researchers mapped autoantorpos of 374 patients with cancer treated with checkpoint immunotherapy, as well as 131 unreed healthy individuals.
The authors of the study intended to better understand the varied answers of patients to a type of immunotherapy that counterblocks the “proteins of checkpointThat prevent a patient’s immune system from attacking cancer cells.
The results, which were published last month in Nature, revealed that naturally occurring autoantibodies can increase or hinder the effectiveness of cancer immunotherapy up to 10 times.
The study was led by Harriet ClugerProfessor of Oncology and Dermatology at Yale School of Medicine, and Aaron Ringwho started the work while in Yale and is now a researcher at Fred Hutchinson Cancer Center.
In the course of the survey, researchers used the Reap (“rapid profile of extracellular antigens) platform to analyze the interaction of antibodies and autoantibodies with proteins on the surface of human cells in sick blood samples.
“This study demonstrates the power of a innovative technology Developed by Dr. Ring when it was in Yale, ”says Kluger in from YSM.” Its Reap platform allows us to study the levels of thousands of autoantibodies in a single experience. “
“When applied to large sets of carefully collected human samples, we can learn a lot about response biology and how to improve our clinical results,” adds the researcher.
Normally, autoantibodies are antibodies that have deviated from their goal – instead of attacking threats to the bodyincluding infectious pathogenic agents such as cancer or viruses, wrongly attack healthy fabric.
However, the results of this study revealed that some autoantibodies in the patients with cancer treated were associated with “drastically altered probabilities” which, in some cases, they helped and, elsewhere, harmed The antitumor efficacy of immunotherapy.
“Our analysis shows that certain autoantibodies that occur naturally cannclinar as probabilities drastically in favor tumors reduction, ”says Aaron Ring.
“We observed some cases where autoantibodies increased the likelihood of a patient responding to the blocking of control points in up to 5 to 10 times. For years, autoantibodies have been seen mainly as harmful agents in the autoimmune diseasebut we are finding that they can also act as powerful and intrinsic therapies“, Details the investigator.
The team found that the interfereautoantibodies that block protein, were associated with better antitumor responses. “In some sick, your immune system essentially produced its own medicine Complementary, ”explains Ring.“ Their autoantibodies have neutralized the interferon and this amplified the effect of control points block – immunotherapy.
“This discovery provides us with a clear plan for combined therapies that intentionally modulate the interferon For all other patients, ”says the investigator.
Not all autoantibodies were beneficial. In some cases, autoantibodies were associated with patients who experienced dramatically reduced benefits from immunotherapy.
Reverse the effects of these antibodies It could restore the effectiveness of immunotherapy in these patients, the study authors say.
“Relations between individual autoantibodies and the impact on immune effectiveness show a deeper interaction What previously knew, ”says Aaron Ring.
“It’s just the beginning. We are now extending research to other cancers and treatments so that we can take advantage of it.
