Immunotherapy has become a rapidly growing segment of cancer treatment with impressive success across aspectrum of malignancies including melanoma, colorectal, and non-small cell lung cancers. Notwithstandingthese advances, a significant fraction of patients fails to respond to immunotherapy and suffers from seriousadverse side effects. While peptide-loaded major histocompatibility complex (pMHC) tetrameric structures allowthe detection of antigen-specific T cells, a few antigen specificities can be detected in parallel because oflimitations on the number of available fluorescent or metal labels. On the other hand, thousands of cells areneeded for the workflow. Improved prognostic methods to monitor the specificity and functional behavior of tumorantigen-specific cytotoxic T cells is greatly needed to enhance the overall effectiveness of a range ofimmunotherapies, especially adoptive cell therapy (ACT), and provide better outcomes for cancer patients.This project develops a first-of-its-kind biosensor platform that enables the rapid and parallel detection of antigen-specific T cells. The proposed lab-on-chip technology allows detection and characterization at a single-cell levelwithout requiring the use of labeling, complicated operational controls, or expensive equipment. As a result, thetechnology can be implemented in point-of-care settings and rapidly provide medical professionals with criticalinformation, such as the ideal timing of future injected doses and any off-target effects. The key innovationsbehind the proposed technology include its high-throughput biosensor architecture, the ability to scale-upmanufacturing using existing silicon foundries, label-free cell detection, simple operation and product design,and the implementation of novel algorithms of robust, real-time data analysis. Moreover, the commercializationof the proposed technology is facilitated by a mature semiconductor industry to achieve this high level ofmultiplexing in a small form factor.The proposed project focuses on engineering and optimization of the proposed biosensor platform and iterativedevelopment using six well-characterized tumor-antigens that are frequently recognized in melanoma patients.Peripheral blood mononuclear cells (PBMCs) from melanoma patients and from healthy donors will be used foranalysis and technology validation. Successful completion of the project will provide a laboratory proof-of-concept, allowing the technology to move forward to a clinical setting where it can be used to monitor patients'ongoing responses to immunotherapy, in specific checkpoint blockade and/or adoptive cell therapy.The tumor profiling market is projected to grow to about $12B by 2024, with the largest sector beingimmunoassays. If successful, the proposed technology will be a groundbreaking development in the cancerimmunology toolbox, especially for early ex vivo identification of resistant tumor cell subpopulations, and helpadvance the effectiveness of cancer treatment for millions of people around the world. Project Narrative This project develops a novel biosensor platform where the combination of high-throughput sensing and single- cell assay capability is expected to lead to a breakthrough in patient outcomes in response to immunotherapy for a wide range of cancers. This project is expected to advance the field of T cell characterization, enhance thousands of clinical trials involving immunotherapy, and enhance the health and wellbeing of millions of cancer and infectious disease patients around the world. Algorithms ; Alleles ; Allelomorphs ; Antibodies ; Antigen-Presenting Cells ; accessory cell ; Antigens ; immunogen ; Architecture ; Engineering / Architecture ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Boston ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Non-Small-Cell Lung Carcinoma ; NSCLC ; NSCLC - Non-Small Cell Lung Cancer ; Non-Small Cell Lung Cancer ; Nonsmall Cell Lung Carcinoma ; nonsmall cell lung cancer ; Cell Adhesion ; Cellular Adhesion ; Cells ; Cell Body ; Chemistry ; Clinical Trials ; Communicable Diseases ; Infectious Disease Pathway ; Infectious Diseases ; Infectious Disorder ; Data Analyses ; Data Analysis ; data interpretation ; Drug Combinations ; Elements ; Engineering ; Engravings ; Equipment ; Flow Cytometry ; Flow Cytofluorometries ; Flow Cytofluorometry ; Flow Microfluorimetry ; Flow Microfluorometry ; flow cytophotometry ; Fluorochrome ; Future ; Glass ; Health ; HLA Antigens ; HL-A Antigens ; Human Leukocyte Antigens ; Leukocyte Antigens ; Immobilization ; orthopedic freezing ; Immunoassay ; Immunotherapy ; Immune mediated therapy ; Immunologically Directed Therapy ; immune therapeutic approach ; immune therapeutic interventions ; immune therapeutic regimens ; immune therapeutic strategy ; immune therapy ; immune-based therapies ; immune-based treatments ; immuno therapy ; Industry ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Major Histocompatibility Complex ; Histocompatibility Complex ; Histocompatibility Complices ; Major Histocompatibility Complices ; Massachusetts ; melanoma ; Malignant Melanoma ; Metals ; Methods ; Fluorescence Microscopy ; Fluorescence Light Microscopy ; Mutation ; Genetic Alteration ; Genetic Change ; Genetic defect ; genome mutation ; Needles ; Optics ; optical ; Patient Monitoring ; Patients ; Peptides ; Personal Satisfaction ; well-being ; wellbeing ; T-Cell Receptor ; MHC Receptor ; Major Histocompatibility Complex Receptor ; Receptors, Antigen, T-Cell ; Refractive Indices ; medical schools ; medical college ; school of medicine ; Semiconductors ; Silicon ; Si element ; Specificity ; T-Lymphocyte ; T-Cells ; thymus derived lymphocyte ; Cytotoxic T-Lymphocytes ; Cell-Mediated Lympholytic Cells ; Cytolytic T-Cell ; Cytotoxic T Cell ; killer T cell ; Technology ; Testing ; Thinness ; Leanness ; Time ; Tumor Antigens ; Tumor-Associated Antigen ; cancer antigens ; tumor-specific antigen ; Universities ; Measures ; Film ; Cell Size ; Label ; sensor ; improved ; Surface ; Clinical ; Phase ; Medical ; prognostic ; peripheral blood ; Collaborations ; fluid ; liquid ; Liquid substance ; Malignant Cell ; cancer cell ; Malignant Pancreatic Neoplasm ; Pancreas Cancer ; Pancreatic Cancer ; pancreatic malignancy ; Malignant neoplasm of pancreas ; Diagnostic ; adoptive cell therapy ; adoptive cellular therapy ; Adoptive Cell Transfers ; Hematologic Cancer ; Hematologic Malignancies ; Hematological Malignancies ; Hematological Neoplasms ; Hematological Tumor ; Hematopoietic Cancer ; Malignant Hematologic Neoplasm ; Hematologic Neoplasms ; Frequencies ; Slide ; In Situ ; Route ; System ; Colon or Rectum ; colo-rectal ; colorectum ; Colorectal ; Tumor Cell ; neoplastic cell ; single cell analysis ; success ; Surface Plasmon Resonance ; PBMC ; Peripheral Blood Mononuclear Cell ; biological sensor ; Biosensor ; Structure ; novel ; UV laboratory microscope ; Ultraviolet Microscopes ; fluorescence/UV microscope ; fluorescent microscope ; laboratory fluorescence light microscope ; fluorescence microscope ; Modeling ; response ; high throughput analysis ; Cancer Treatment ; Malignant Neoplasm Therapy ; Malignant Neoplasm Treatment ; anti-cancer therapy ; anticancer therapy ; cancer-directed therapy ; cancer therapy ; cancer immunology ; neoplasm immunology ; tumor immunology ; cancer diagnosis ; T Cell Specificity ; T-Cell Immunologic Specificity ; Malignant Ovarian Neoplasm ; Malignant Ovarian Tumor ; Malignant Tumor of the Ovary ; Ovary Cancer ; ovarian cancer ; Malignant neoplasm of ovary ; T-Cell Activation ; µfluidic ; Microfluidics ; Effectiveness ; photonics ; GP100 ; ME20 ; Melanocyte Protein 17 ; Mouse Homolog of SILVER ; PMEL gene ; PMEL protein ; PMEL17 ; Premelanosomal Protein ; SILV protein ; SILV gene ; Address ; Dose ; DF/HCC ; Dana-Farber Cancer Institute ; Detection ; Melanoma Cell ; Resolution ; Cancer Patient ; Cellular Assay ; cell assay ; Optical Instrument ; Optics/Optical Instrument ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; technology validation ; technology implementation ; Monitor ; Development ; developmental ; point of care ; Output ; digital ; rapid detection ; design ; designing ; Outcome ; Population ; innovation ; innovate ; innovative ; Resistance ; resistant ; prototype ; commercialization ; tumor ; standard of care ; manufacturing scale-up ; operation ; imaging system ; immune checkpoint blockade ; check point blockade ; checkpoint blockade ; immune check point blockade ; antigen-specific T cells ; tumor behavior ; side effect ; engineered T cells ; chimeric antigen receptor T cells ; CAR T cells ; T cells for CAR ; chimeric antigen receptor (CAR) T cells ; refractory cancer ; resistant cancer ; antigen detection ; antigen based detection ; detect antigen ; detection platform ; detection system ;
