Researchers believe an assay may be used to detect and monitor dynamics of genetic mutations of patients treated with immunotherapy.
It may be possible to use bioinformatics as a gathering tool to determine how a patient’s immune system responds to immunotherapy. In a study published in Cancer Immunology Research, researchers at the Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy report that an assay may be used as a molecular barcode to detect and monitor the dynamics of genetic mutations in blood, tumor, and normal tissue of patients receiving immunotherapy.
Mutation-associated neoantigens (MANAs) are a target of antitumor T-cell immunity. However, there has been a need to find out how well T cells can recognize these MANAs in cancer patients. The authors of the study note that assays analyzing in vitro cytokine production, such as enzyme-linked immunospot and intracellular cytokine staining, have been very useful. However, the researchers write that those assays have limited sensitivity in assessing tumor-specific T-cell responses. In addition, these assays do not analyze antigen-specific T-cell repertoires.
It is hoped that a sensitive, simple, and standardized assay could be used that can assess the repertoire of functional MANA-specific T cells. The researchers describe in their paper the FEST (Functional Expansion of Specific T cells) assay, which integrates T-cell antigen receptor sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform. This allows for the identification of antigen-specific clonotypic amplifications.
“MANAFEST is a test that can detect a patient’s immune response to their tumor. This test is particularly important because immunotherapy relies on the patient’s immune response to clear the tumor after treatment. Using MANAFEST to detect the pre-existing immune response, or the immune response induced immediately after treatment, could help inform treatment decisions and could eventually be used as a biomarker to predict which patients are likely to respond,” said senior study author Kellie Smith, PhD, of Johns Hopkins Kimmel Cancer Center in Baltimore.
MANAFEST is compatible with high-throughput routine clinical and lab practices, according to the researchers. Currently, the MANAFEST assay “is pretty solid” in its current form, according to Smith. However, she said there is still a long way to go before it can be used in the clinic.
“We are currently developing massive relational databases to link the results of the assay with things like clinical outcome, demographic parameters, development of immune-related adverse events, etc. The beauty of MANAFEST is that it provides a wealth of data. The limitation is that we now have to figure out how to use this goldmine effectively to help patients,” Smith told Cancer Network.
Sebastiano Battaglia, PhD, assistant professor of oncology at the Center for Immunotherapy at Roswell Park Comprehensive Cancer Center in Buffalo, said this is an important first step and may have significant clinical implications. “This study illustrates a practical example of actionable and novel diagnostic opportunities from the application of ‘Big Data’ approaches to clinical challenges, in this case in the form of deep profiling of the tumor and the patient’s lymphocytes. Furthermore, it underscores how proactive communication between scientists and clinicians can open the door to strategies with potential to revolutionize cancer therapeutics,” he told Cancer Network.