SEQUENCE-BASED MEASURES OF IMMUNE RESPONSE

摘要

The invention is directed to methods of measuring an immune response by comparing sequence-based clonotype frequency data from successively measured clonotype profiles. In particular, the invention includes immunotherapies of cancers, such as lymphomas, that include sensitive pre- and post-vaccination sequence-based measurements of changes in a patient's immune repertoire, thereby providing a sensitive measure of the likelihood of treatment success.

主权项

1. A method of determining a level of immune response in an individual to a treatment, the method comprising the steps of:
(a) obtaining at least one first sample from the individual prior to the treatment and at least one second sample from the individual after the treatment, the first and second samples comprising T-cells and/or B-cells; (b) amplifying molecules of nucleic acid from the T-cells and/or B-cells of the first and second samples, the molecules of nucleic acid comprising recombined DNA sequences from T-cell receptor genes or immunoglobulin genes; (c) sequencing the amplified molecules of nucleic acid to form a first clonotype profile of the first sample and second clonotype profile of the second sample; (d) assigning a rank to clonotypes of each of the first and second clonotype profiles based on their frequency of occurrence; and (e) determining a correlation between ranks of clonotype frequencies of the first clonotype profile to those of the second clonotype profile, wherein a level of immune response to the treatment is inversely related to such correlation.