Antibody and T-cell receptor sequencing for identifying cancer-specific immune receptors

This tech identifies cancer-specific antibodies and T-cell receptors by sequencing mRNA from immune cells in a patient’s tumor-draining lymph nodes and comparing the sequences with the patient’s antibody polypeptide data.

Background

Cancer immunotherapy has emerged as a promising approach to treating various types of cancers. This field leverages the body’s own immune system to target and eliminate cancer cells, offering the potential for highly specific and effective treatments with fewer off-target effects compared to traditional therapies like chemotherapy and radiation.

The development of therapeutic antibodies, such as Herceptin, Rituxan, and Avastin, has demonstrated the life-saving potential of immunotherapy. However, the identification of biologically relevant antibodies and T-cell receptors that exhibit a beneficial effect in controlling diseases remains a significant challenge.

Current methods for identifying and characterizing antigen-specific antibodies or T-cell receptors directly from a patient are limited by several factors. Traditional techniques, such as hybridoma technology and single B cell cloning, are often labor-intensive, time-consuming, and may not accurately reflect the diversity and abundance of antibodies in a patient’s serum. Additionally, these approaches often focus on specific stages of B cell development, potentially overlooking key antibody-producing cells.

Moreover, existing methods struggle to provide comprehensive information on the serum concentration and clonal abundance of specific antibodies, hindering the development of truly effective polyclonal antibody therapies.

Technology description

This technology describes a method for identifying cancer-specific antibodies and T-cell receptors. It involves isolating mRNA sequences from individual B-cells and T-cells obtained from a patient’s tumor-draining lymph nodes. These sequences encode the paired variable heavy (VH) and light (VL) chains for antibodies, or the T-cell receptor polypeptides.

By comparing these sequences with mass spectrometry data of peptides derived from the patient’s antibodies, the method pinpoints the exact amino acid sequences that make up cancer-specific antibodies or T-cell receptors. The technology also encompasses the production of these identified molecules and the potential development of chimeric antigen receptors based on them.

This method is differentiated by its ability to identify and quantify tumor-specific antibodies directly from a patient’s lymph nodes, a rich source of immune cells actively engaged in fighting the cancer. This approach bypasses the need for traditional hybridoma technology or B-cell immortalization techniques, which can be time-consuming and may not accurately reflect the antibodies present in the patient’s serum.

By combining high-throughput sequencing of immune receptor repertoires with mass spectrometry analysis, this technology offers a comprehensive and efficient way to discover novel antibodies that can target specific cancer antigens, paving the way for personalized cancer therapies.

Benefits

Identifies tumor-specific antibodies and T-cell receptors
Utilizes paired mRNA sequencing from individual immune cells in sentinel lymph nodes
Compares sequences with mass spectrometry data from cancer patients
Isolates mRNA sequences from B-cells and T-cells, specifically from tumor-draining lymph nodes
Identifies amino acid sequences encoding cancer-specific antibodies or T-cell receptors
Enables production of identified molecules and potential development of chimeric antigen receptors
Facilitates high-throughput sequencing of immune receptor repertoires
Allows discovery of novel antibodies targeting specific cancer antigens, such as NY-ESO-1