Publications by authors named "Katharine Heeringa"

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy.

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Article Synopsis
  • T cell receptors (TCRs) are crucial for T cells to detect cancer cell mutations, and researchers used a CRISPR-Cas9 method to edit TCR genes in a clinical trial setting.
  • Sixteen patients with advanced solid cancers received personalized T cell therapies featuring engineered neoTCRs, with most participants experiencing either stable disease or disease progression.
  • The study confirmed that it is feasible to create multiple engineered TCRs, showing the safety and effectiveness of infusing gene-edited T cells that can successfully target tumors.
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The expression analysis of recombinant proteins is a challenging step in any high-throughput protein production pipeline. Often multiple expression systems and a variety of expression construct designs are considered for the production of a protein of interest. There is a strong need to triage constructs rapidly and systematically.

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Molecularly engineered antibodies with fit-for-purpose properties will differentiate next generation antibody therapeutics from traditional IgG1 scaffolds. One requirement for engineering the most appropriate properties for a particular therapeutic area is an understanding of the intricacies of the target microenvironment in which the antibody is expected to function. Our group and others have demonstrated that proteases secreted by invasive tumors and pathological microorganisms are capable of cleaving human IgG1, the most commonly adopted isotype among monoclonal antibody therapeutics.

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