Utilizing Bioinformatics to Determine a Patient's Response to Immunotherapy

Recently, researchers conducted a study at Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy that discovered a new way to use bioinformatics to determine how a patient’s immune system responds to immunotherapy.

Mutation-associated neoantigens (MANAs) are a target of antitumor T-cell immunity. However, previously there was no way to identify how well T cells can recognize these MANAs in patients with cancer. “Sensitive and specific T-cell assays that assess the repertoire of MANA-specific T cells are needed to understand the nature of antitumor immunity and to identify biomarkers predictive of response to immunotherapies,” stated the study.

The researchers were able to change how cultures were obtained in order to improve the accuracy of the data collected for bioinformatics. This process created the Functional Expansion of Specific T-cells (FEST) analysis. FEST “integrates TCR [T-cell receptor] sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications,” noted the authors. The researchers are looking to combine this information in the creation of a database to investigate what types of immunotherapy-related responses are associated with clinical benefit.

“Once people are diagnosed with cancer, we hope to use this procedure to develop the best treatment options for them,” said Kellie Smith, PhD, senior author of the study and instructor of oncology at Johns Hopkins Kimmel Cancer Center, in a statement.

The FEST analysis was adapted to be able to detect a MANA-specific sequence in blood, tumors, and normal tissue of patients receiving immunotherapy treatment. This technique, the authors noted, could be used to predict patient responses to immunotherapy in many different cancers.

Due to the development of personalized cancer therapies, researchers noted there is now a need for routine high-throughput assays that monitor the antitumor immune response.

“MANAFEST brings scientific and translational value, owing to the capacity for molecular characterization of the TCR sequences associated with MANA recognition that can be coordinated across patients or histologies and between institutions to identify common genomic features associated with immunogenicity of tumors and common structural motifs of the TCR,” noted the study authors.

in looking to the future, the authors hope the test will lead to a conglomerate of data that would be able to monitor how well patients with cancer respond to immunotherapy treatments.

Reference

Danilova L, Anagnostou V, Caushi J, et al. The mutation-associated neoantigen functional expansion of specific T cells (MANAFEST) assay: a sensitive platform for monitoring antitumor immunity [published online June 12, 2018]. Cancer Immunol Res. doi: 10.1158/2326-6066.CIR-18-0129.