Research

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:

• Renal cell carcinoma (RCC) [NCT02950766]
• Glioblastoma multiforme (GBM) [NCT02287428]
• Ovarian cancer [NCT04024878]
• Melanoma [NCT03929029]
• Chronic leukemia and lymphoma (CLL) [NCT03219450]
• Follicular lymphoma (FL) [NCT03361852]

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

• Directing traffic: how to effectively drive T cells into tumors (Cancer Discov. 2020)
• Automated Flow Synthesis of Tumor Neoantigen Peptides for Personalized Immunotherapy (Sci. Rep. 2020)
• RNase H-dependent PCR-enabled T-cell receptor sequencing for highly specific and efficient targeted sequencing of T-cell receptor mRNA for single-cell and repertoire analysis (Nat. Protoc. 2019)
• Cancer Vaccines: Steering T Cells Down the Right Path to Eradicate Tumors (Cancer Discov. 2019)
• Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial (Nature 2018)
• A cloning and expression system to probe T cell receptor specificity and assess functional avidity to neoantigens (Blood 2018)
• Immunotherapy for glioblastoma: going viral (Nat. Med. 2018)
• Acquired mechanisms of immune escape in cancer following immunotherapy (Genome Med. 2018)
• Towards personalized, tumour-specific, therapeutic vaccines for cancer (Nat. Rev. Immunol. 2018)
• An immunogenic personal neoantigen vaccine for patients with melanoma (Nature 2017)
• Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction (Immunity 2017)
• Predicted neoantigen load in non-hypermutated endometrial cancers: Correlation with outcome and tumor-specific genomic alterations (Gynecol. Oncol. Rep. 2017)
• Landscape of tumor-infiltrating T cell repertoire of human cancers (Nat. Genet. 2016)
• Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes (Nat. Biotechnol. 2015)
• Immunotherapy advances for glioblastoma (Neuro Oncol. 2014)
• Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia (Blood 2014)
• HLA-binding properties of tumor neoepitopes in humans (Cancer Immunol. Res. 2014)
• Vaccines and melanoma (Hematol. Oncol. Clin. North Am. 2014)
• Personal neoantigen cancer vaccines: The momentum builds (Oncoimmunology 2014)
• Getting personal with neoantigen-based therapeutic cancer vaccines (Cancer Immunol. Res. 2014)