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Principal Investigator: Blaine McCarthy
Organization: STANFORD UNIVERSITY
Fiscal Year: 2021
Award: $65,610
Funding agency: National Cancer Institute
Cancer vaccines have the potential to provide potent and personalized therapeutics with long-lasting
effects for treatment of the ~100 million people worldwide currently affected by this disease. While recent
advances have led to the first FDA-approved cancer vaccines, treatments that are broadly effective across
patient populations remain elusive. As such, there is a critical need to develop cancer vaccines that operate via
fundamentally new mechanisms that enable greater potency. The overall goal of this work is to leverage recent
advances in gene delivery and cell reprogramming to develop a cancer vaccine that directly reprograms cancer
cells into anti-tumor immune cells. The proposed work will be executed in the lab of Prof. Robert Waymouth
(chemistry) at Stanford and in close collaboration with Prof. Paul Wender (chemistry), Prof. Ravindra Majeti
(medicine), and Prof. Ronald Levy (medicine). Through this interdisciplinary collaboration of chemists and cancer
immunologists, vaccines that operate by a unique cell reprogramming mechanism will be developed and the
efficacy of these vaccines will be evaluated in cell lines and vertebrate models.
One critical barrier that hinders the potency of current cancer vaccination approaches is insufficient activation
of immune cells (T cells) due to inefficient antigen presentation or lack of costimulatory signals. To overcome
this barrier, a new cancer vaccination strategy will be developed that directly reprograms cancer cells into
immune cells that exhibit cancer-derived antigens and the proper costimulatory molecules for efficient T cell
activation. To realize this goal, gene delivery vehicles will be developed for cancer cell reprogramming and
relationships between their molecule structure and function (i.e. protein expression and biodistribution) will be
elucidated (Aim 1). These gene delivery vehicles will be used to reprogram cancer cells into antigen presenting
cells (APCs) using cell lines and vertebrate models (Aim 2). The ability of reprogrammed APCs to elicit a cancer-
targeted immune response and establish immunological memory will be investigated (Aim 3). These studies are
anticipated to lay the groundwork for future application of this technology in the clinic and add to the growing
body of knowledge on gene delivery, cell reprogramming, and cancer vaccine development. In line with the
mission of the NIH, the fundamental knowledge and therapeutic technology developed through this work will
improve the future of human health by helping to treat cancer, one of the most prevalent and deadly diseases.
The candidate will use this postdoctoral training fellowship to grow as an intellectual and researcher in the
biological sciences by learning a suite of new experimental techniques and theoretical concepts that compliment
her expertise in chemistry. The unique support provided by this fellowship, the chosen sponsor (Prof.
Waymouth), key collaborators (Professors Wender, Majeti, and Levy), and research institution (Stanford) will
enable the applicant to progress as a researcher and mentor and engage in professional development activities
to accelerate the trajectory of her future career towards becoming a professor at an R1 institution.
Terms: <Active Immunotherapy><Address><Affect><Antibodies><Antigen Presentation><Antigen-Presenting Cells><Antigens><Antineoplastic Vaccine><Basal Transcription Factor><Basal transcription factor genes><Biodistribution><Biologic Sciences><Biological Sciences><Bioscience><Bp50><C-EBP alpha><C-EBP α><C-EBPalpha><C-EBPα><CCAAT-Enhancer-Binding Protein-alpha><CCAAT-Enhancer-Binding Protein-α><CD40><CD86><CD86 gene><CDW40><Cancer Genes><Cancer Treatment><Cancer Vaccine Related Development><Cancer Vaccines><Cancer-Promoting Gene><Cancers><Cations><Cell Body><Cell Communication and Signaling><Cell Culture Techniques><Cell Line><Cell Signaling><CellLine><Cells><Cellular biology><Charge><Chemistry><Class I Genes><Clinic><Collaborations><Development><Disease><Disorder><Exhibits><FDA approved><Fellowship><Future><Gene Delivery><General Transcription Factor Gene><General Transcription Factors><Genes><Genetic><Genetic Vectors><Genome><Goals><Health><Human><Immune><Immune Cell Activation><Immune Targeting><Immune infiltrates><Immune mediated therapy><Immune memory><Immune response><Immune system><Immunes><Immunologic Memory><Immunological Memory><Immunological response><Immunologically Directed Therapy><Immunologist><Immunooncology><Immunotherapy><Institution><Intracellular Communication and Signaling><Investigation><Investigators><Knowledge><Learning><Life Sciences><MGC9013><MHC Class I><MHC Class I Genes><Malignant Cell><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Mediating><Medicine><Mentors><Messenger RNA><Methods><Mission><Modeling><Modern Man><Modification><Myelogenous><Myeloid><Mφ><NIH><National Institutes of Health><Neoplasm Vaccines><Nucleic Acids><Oncogenes><Organism><Patients><Proteins><RNA vaccine><RNA-based vaccine><Research><Research Personnel><Researchers><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Strains Cell Lines><Structure><T cell infiltration><T cell tumor trafficking><T-Cell Activation><T-Cells><T-Lymphocyte><TNFRSF5><TNFRSF5 gene><Techniques><Technology><Teff cell><Therapeutic><Transcription Factor Proto-Oncogene><Transcription factor genes><Transforming Genes><Tumor Cell><Tumor Necrosis Factor Receptor Superfamily Member 5 Gene><Tumor Vaccines><Tumor-infiltrating immune cells><United States National Institutes of Health><Vaccination><Vaccines><Work><accessory cell><allergic/immunologic body system><allergic/immunologic organ system><anamnestic reaction><anti-cancer immunotherapy><anti-cancer therapy><anti-tumor vaccine><anticancer immunotherapy><anticancer therapy><antitumor vaccine><base><biological signal transduction><cancer cell><cancer immunotherapy><cancer therapy><cancer vaccination><cancer vaccine development><cancer-directed therapy><career><cell biology><cell culture><cultured cell line><deliver vaccines><design><designing><develop a vaccine><development of a vaccine><developmental><effector T cell><gene therapeutics><gene-based therapeutic><gene-based therapeutics><genes therapeutic><genes therapeutics><host response><immune activation><immune cell infiltrate><immune infiltration><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based cancer therapies><immune-based therapies><immune-based treatments><immune-oncology><immuno oncology><immuno therapy><immunogen><immunology oncology><immunoresponse><immunotherapy for cancer><immunotherapy of cancer><improved><in vivo><innovate><innovation><innovative><insight><interdisciplinary collaboration><intratumoral immune cell><lipophilicity><living system><mRNA><mRNA vaccine><mRNA-based vaccine><macrophage><malignancy><neoplasm/cancer><neoplastic cell><novel><oncoimmunology><p50><patient population><personalized therapeutic><post-doctoral training><postdoctoral training><professor><protein expression><secondary immune response><stem><therapeutic gene><thymus derived lymphocyte><transcription factor><transdisciplinary collaboration><transfection vector><treatment effect><treatment strategy><tumor><tumor immune cell><tumor vaccination><vaccination strategy><vaccine delivery><vaccine development><vaccine efficacy><vaccine for cancer><vaccine formulation><vector>