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Clinical Trials and Discovery Science

    In this section

    Clinical Trials of Personal Cancer Vaccines

    In our first iteration of clinical trials, we tested the vaccine in the adjuvant setting for solid tumors (Ott and Hu Nature 2017; Keskin and Anandappa Nature 2019). Building on our first-in-human clinical trials in melanoma and glioblastoma, the existing long peptide vaccine is being further investigated in the clinical setting in these and several additional tumor types, including those in the active setting of malignancy:

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    Vaccines targeting tumor mutations require personalization for each patient
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    Peripheral blood phenotype and distribution of CD4+ intratumoral TCR clonotypes
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    Antigen specificity of TCRs from CD4+ TILs

    Discovery Science

    We have established the clinical as well as the laboratory infrastructure for undertaking personal cancer vaccine studies at Dana-Farber. Discovery research and technology development are critical in improving vaccine design, response, and manufacture so we can continue increasing the proportion of patients who can benefit from immunotherapy. Learning more about how the immune system responds to the vaccine will help inform both vaccine development as well as how clinical trial studies are conducted.

    Optimizing Vaccine Design

    We have a deep commitment to developing more accurate and precise prediction tools to optimize neoantigen discovery using machine learning algorithms and proteomics (see Abelin and Keskin Immunity 2017; Sarkizova and Klaeger Nature Biotechnology 2020).

    Understanding the Immune Response

    In conjunction with the Translational Immunogenomics Lab (TIGL), we have created high-resolution immunogenomic tools to allow in-depth assessment of NeoVax-induced immune responses. We use genomics (often at the single-cell level), proteomics, molecular immunology, and computational methods to study TCRs as well as antigen-specific interactions and their involvement in pathways underling anti-tumor immunity.

    Improving the Efficiency of Peptide Manufacture

    Fundamental issues with vaccine manufacture include the high cost and long timelines for personalized production. To accelerate manufacturing of our peptide vaccines, we are working with Bradley Pentelute and other investigators at MIT to optimize this process by using automate fast-flow synthesis (Truex et al Scientific Reports 2020).

    Research Publications by Our Experts

    2023

    Dynamics and specificities of T cells in cancer immunotherapy | Nature Reviews Cancer (Nature 2023)

    2022
    Improved T-cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer - PubMed (nih.gov) (Clin Cancer Res. 2022)
    Cancer vaccines: Building a bridge over troubled waters - PubMed (nih.gov) (Cell 2022)
    Landscape of helper and regulatory antitumour CD4+ T cells in melanoma | Nature (Nature 2022)

    2021

    Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma | Nature (Nature 2021)

    2014-2020

    Thanks to Our Supporters

    We are grateful to the people and organizations that have supported our research: