The General Hospital Corporation

Dana-farber-cancer Institute Inc.

The Broad Institute, Inc.

Harvard College

Catherine Ju-Ying Wu

Nir Hacohen

Gad Getz

Edward F Fritsch

Alexander Meissner

Ute E Burkhardt

Mark Kendell Clement

Dan-Avi Landau

Sachet Ashok Shukla

The present disclosure relates to methods for profiling subject specific and personalized T cell receptor (TCR) repertoires using a single-cell sequencing method. More particularly, disclosed are methods for determining binding of T cell receptors to subject specific neoantigens. In addition, the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens. Moreover, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers and therapies. Finally, cloned TCRs can be used to formulate personalized immunotherapies for those inflicted with a disease, such as cancer.

Methods for profiling the T-cell-receptor repertoire

The present invention relates to methods of determining a cancer treatment prognosis for a subject in need thereof by evaluating epigenetic and genetic changes within a tumor sample from the subject. The present invention further provides methods of treating cancer in a subject by evaluating epigenetic and genetic changes within a tumor sample from the subject. In addition, the present invention provides methods of screening test agents to identify agents that decrease tumor cell plasticity.

Compositions and methods for diagnosing, evaluating and treating cancer by means of the DNA methylation status

A system and method for determining the exact pair of alleles corresponding to polymorphic genes from sequencing data and for using the polymorphic gene information in formulating an immunogenic composition. Reads from a sequencing data set mapping to the target polymorphic genes in a canonical reference genome sequence, and reads mapping within a defined threshold of the target gene sequence locations are extracted from the sequencing data set. Additionally, all reads from the set data set are matched against a probe reference set, and those reads that match with a high degree of similarity are extracted. Either one, or a union of both these sets of extracted reads are included in a final extracted set for further analysis. Ethnicity of the individual may be inferred based on the available sequencing data which may then serve as a basis for assigning prior probabilities to the allele variants. The extracted reads are aligned to a gene reference set of all known allele variants. The allele variant that maximizes a first posterior probability or posterior probability derived score is selected as the first allele variant. A second posterior probability or posterior probability derived score is calculated for reads that map to one or more other allele variants and the first allele variant using a weighting factor. The allele that maximizes the second posterior probability or posterior probability score is selected as the second allele variant. A system and method for identifying somatic changes in polymorphic loci using WES data. The exact pair of alleles corresponding to the polymorphic gene are determined as described using a normal or germline sample from an individual. A tumor or otherwise diseased sample is also retrieved from the individual and the corresponding WES data is generated. Reads corresponding to the polymorphic gene are extracted as described in the paragraph above. These reads are then aligned to the inferred pair of allele sequences. The alignment of the germline or normal reads to the inferred pair of alleles, along with the alignment of the tumor or diseased reads to the inferred pair of alleles are simultaneously used as inputs to somatic change detection algorithms to identify somatic changes with greater precision and sensitivity.

Polymorphic gene typing and somatic change detection using sequencing data

Methods for profiling the t cell repertoire

Compositions and methods for diagnosing, evaluating and treating cancer

The present invention related to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. Specifically, the invention provides a method of identifying tumor specific neoantigens that alone or in combination with other tumor-associated peptides serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor responses.

Compositions and methods of identifying tumor specific neoantigens

Growing community of inventors

Brookline, MA, United States of America

Catherine Ju-Ying Wu