Researchers at the Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy developed a new way to use bioinformatics as a gathering tool to determine how a patient's immune system responds to immunotherapy and recognizes its own tumor.

Mutation-associated neoantigens (MANA) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology.

Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires.

The FEST (Functional Expansion of Specific T cells) assay described herein integrates T-cell receptor sequencing of short-term, peptide-stimulated cultures with a bioinformatics platform to identify antigen-specific clonotypic amplifications. This assay can be adapted for all types of antigens, including MANAs via tumor exome-guided prediction of MANAs.

Senior author Kellie Smith, Ph.D., instructor of oncology at Johns Hopkins Kimmel Cancer Center, hopes enough data can be recovered to allow clinicians to determine the best course of treatment for patients by using a technique called MANAFEST.

"Once people are diagnosed with cancer, we hope to use this procedure to develop the best treatment options for them," Smith said. "Previously, the technology (for MANAFEST) was not there. In the last few years, the technology has evolved to enable us to come up with the way to analyze the data to help patients."

Mutation-associated neoantigens

Mutation-associated neoantigens (MANAs) are a target of antitumor T-cell immunity. However, there was a need to find out how well T-cells can recognize these MANAs in cancer patients.

The scientists changed how cultures were gathered to improve the accuracy of data for bioinformatics, creating the FEST (Functional Expansion of Specific T-cells) analysis.

They said this combined information could be used to create a database to figure out what types of immunotherapy-related responses are associated with clinical benefit, improving the effectiveness of treatment for patients.

The FEST method was explicitly adapted to detect a MANA-specific sequence in blood, tumor and normal tissue of patients receiving immunotherapy. Smith said the technique could be used to serve as a predictor of responses to immunotherapy in many types of cancers.

She cautioned this is only the first generation for FEST to be used. The hope is it will lead to a central repository of data that could monitor how well cancer patients mount immune responses to their disease.