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A Tool for Understanding Human Immunoglobulin Genomic Variants as Predictive Biomarkers of Antibody Response

A method to fully sequence and genotype genetic variation in the human immunoglobulin (IG) heavy chain.

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Project Overview

  • The human immunoglobulin (IG) genetic variation is one of the most difficult and diverse loci in the genome, challenging the capacity to understand the genomic variation in these regions and making it difficult to understand how individuals mount a functional antibody response.
  • This knowledge can be important for the treatment of cancers such as B-cell chronic lymphocytic leukemia (B-CLL). Therefore, there is a need to better understand the biology of IG loci, its diversity, and its link to antibody variability.
  • Dana-Farber scientists have created a new assay for fully characterizing IG heavy chain genetic variation.
  • This technology is available for licensing or for further development with collaborators and commercial partners.

Technology

Researchers from the Dana-Farber Cancer Institute have developed a method to fully sequence and genotype genetic variation in the human IG heavy chain (IGH), which allows descriptions of allelic variants within the IGH variable (IGHV), joining (IGHJ) and diversity (IGHD) gene segments as well as nucleotide and structural variants. This assay is accompanied by an informatic tool to process the sequencing data.

The team has developed a human anti-idiotypic monoclonal antibody (huG6), which may provide a new precision medicine to selectively kill B-cells expressing IGHV1-69 B cell receptors. Other treatments, such as Campath, result in the global depletion of B cells. 

Benefits of the technology:

  • This method allows for entire IG locus interrogation and examination.
  • IG genomic data will help better understand and predict antibody-driven responses.
  • This method and informatics pipeline can now be extended to cover the IG light chain gene regions, as well as the T cell receptor gene loci.
  • HuG6 antibody is the first human anti-idiotypic mAb antibody that may provide new precision medicine to selectively kill IGHV1-69 encoding G6-id+ B-CLL cells. 

Team Members: Wayne Marasco, MD, PhD, Corey Watson, PhD

Applications

  • Predictive insights into antibody-driven responses of specific individuals thanks to our knowledge of IG variation.
  • Vaccine design can be a potential application if specific antibody responses are desired.
  • HuG6 antibody can be used as a precision medicine against a subgroup of B-CLL patients, compared to other treatments that result in the global depletion of B cells.

Opportunities

Dana-Farber is seeking a development partner, commercial partner, or to license the technology. 

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Team Members