Document text
Principal Investigator: Melissa Berrien Elliott
Organization: SAINT LOUIS UNIVERSITY
Fiscal Year: 2024
Award: $186,030
Funding agency: National Cancer Institute
PROJECT SUMMARY
Candidate: During my training, I have been highly motivated to understand how cytotoxic lymphocytes can be
used as an adoptive therapy and how immune cells are regulated during immunotherapy. I have served as first,
co-, and corresponding author on numerous high-impact original research articles, representing advances in
basic, translational, and clinical immunology. I have successfully competed for career development awards that
have allowed me to continue my research interests. My long-term research goals are to understand the
mechanisms important for NK cell effector functions, how NK cells contribute to and are impacted by
immunomodulation and how host immune responses can promote or limit their NK cells as an effective cellular
therapy in human and murine systems.
Research Career Development Plan: As I begin my independent research program, I will utilize educational
and research resources aimed specifically at junior faculty at Washington University to strengthen my career
development. While I have the scientific training and expertise to perform the proposed studies, I will utilize the
opportunities at WUSM to prepare for my tenure-track position. Specifically, aspects of management,
mentorship, and the learning the administrative responsibilities of running a research laboratory (animal
protocols, institutional approvals, budget management).
Research Project: The long-term goal of this project is to improve our understanding of mechanisms operative
in the successes and failures of innate immune therapy. Memory-like NK cells were first identified in mice over
a decade ago and studies examining their persistence, anti-tumor responses, and metabolic adaptations to the
tumor microenvironment have laid the groundwork for both the human trials currently open to enrollment and the
studies proposed herein. One current barrier in the field is translating these novel immune approaches which
have had so much success in treating hematologic malignancies into successes treating solid tumors. We
hypothesize that ML NK cell differentiation combined with chimeric antigen receptor (CAR)-targeting will improve
NK cell trafficking, effector responses, and fitness in both allogeneic and autologous immunotherapeutic
paradigms. We will evaluate this concept against cancer and infection. These studies may reveal novel strategies
or therapeutic interventions for NK-cell based therapies that will likely be broadly relevant to other cellular
therapies. Completion of these studies will lay the scientific groundwork for both future R01 applications and for
a successful career studying the interactions of adoptive cell therapy and the host immune system.
Terms: <Address><Adoptive Cell Transfers><Allogenic><Animals><Antigens><Antitumor Response><Assay><Autologous><Bioassay><Biologic Models><Biological Assay><Biological Models><Budgets><CAR T cells><CAR modified T cells><CAR-T><CAR-Ts><Cancer Patient><Cancer Treatment><Cancers><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Cell Body><Cell Differentiation><Cell Differentiation process><Cell Therapy><Cells><Cellular biology><Chemotactic Cytokines><Clinic><Clinical><Clinical Immunology><Clinical Trials><Clinical Trials Design><Cytotoxic cell><Development><Development Plans><Disease><Disorder><Economics><Edodekin Alfa><Effector Cell><Emergent Technologies><Emerging Technologies><Endowment><Enrollment><Environment><Explosion><Faculty><Failure><Future><Gene Modified><Genes><Goals><Hematologic Cancer><Hematologic Malignancies><Hematologic Neoplasms><Hematological Malignancies><Hematological Neoplasms><Hematological Tumor><Hematopoietic Cancer><Heterograft><Heterologous Transplantation><Homing><Homologous Chemotactic Cytokines><Human><IFN-Gamma-Inducing Factor Gene><IFN-gamma-Inducing Factor><IGIF><IGIF Gene><IL-1 Gamma><IL-1 Gamma Gene><IL-12><IL-15><IL-18><IL-18 Gene><IL-1g><IL-1g Gene><IL12><IL15><IL15 Protein><IL18><IL18 Protein><IL18 gene><IL1F4><IL1F4 Gene><Immune><Immune mediated therapy><Immune response><Immune system><Immunes><Immunochemical Immunologic><Immunocompetent><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic><Immunological><Immunological response><Immunologically><Immunologically Directed Therapy><Immunologics><Immunomodulation><Immunosuppressed Host><Immunotherapeutic agent><Immunotherapy><In Vitro><In vivo analysis><Infection><Infection Control><Institution><Intercrines><Interferon-Gamma-Inducing Factor Gene><Interferon-gamma-Inducing Factor><Interleukin 18 (Interferon-Gamma-Inducing Factor)><Interleukin 18 (Interferon-Gamma-Inducing Factor) Gene><Interleukin 18 Proprotein><Interleukin 18 Proprotein Gene><Interleukin-1 Gamma><Interleukin-1 Gamma Gene><Interleukin-12><Interleukin-15><Interleukin-15 Precursor><Interleukin-18><Interleukin-18 Precursor><Interleukin-18 Precursor Gene><Intrinsic factor><K lymphocyte><K-Awards><K-Series Research Career Programs><Laboratory Research><Learning><Lymphatic cell><Lymphocyte><Lymphocytic><MGC12320><MGC12320 Gene><MGC9721><Malignant Hematologic Neoplasm><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Memory><Mentorship><Metabolic><Mice><Mice Mammals><Model System><Modern Man><Molecular><Murine><Mus><NK Cells><NKSF><Natural Killer Cell Stimulatory Factor><Natural Killer Cells><Outcome><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Phenotype><Position><Positioning Attribute><Process><Production><Property><Protocol><Protocols documentation><R-Series Research Projects><R01 Mechanism><R01 Program><Receptor Protein><Research><Research Career Program><Research Grants><Research Project Grants><Research Projects><Research Resources><Resistance><Resources><Running><SIS cytokines><Safety><Sampling><Solid Neoplasm><Solid Tumor><Specificity><System><T cells for CAR><T-Cells><T-Lymphocyte><Testing><Therapeutic Agents><Toxic effect><Toxicities><Training><Translating><Universities><Viral Diseases><Virus Diseases><Washington><Work><Xenograft><Xenograft procedure><Xenotransplantation><adoptive cell therapy><adoptive cellular therapy><anti-cancer therapy><anti-tumor response><anti-viral efficacy><cancer microenvironment><cancer therapy><cancer-directed therapy><career><career development><cell biology><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular differentiation><cellular therapeutic><cellular therapy><chemoattractant cytokine><chemokine><chimeric antigen T cell receptor><chimeric antigen receptor><chimeric antigen receptor (CAR) T cells><chimeric antigen receptor T cells><chimeric antigen receptor fusion protein T-cells><chimeric antigen receptor modified T cells><cytokine><cytotoxic><design><designing><determine efficacy><developmental><economic><education resources><educational resources><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><enroll><evaluate efficacy><examine efficacy><experiment><experimental research><experimental study><experiments><fitness><flexibility><flexible><gene modification><genetically modified><host response><immune competent><immune drugs><immune modulation><immune regulation><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapeutics><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunologic reactivity control><immunologic therapeutics><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><immunosuppressed patient><immunotherapeutics><immunotherapy agent><improved><in vitro activity><in vivo><in vivo evaluation><in vivo testing><interest><lymph cell><malignancy><mouse model><murine model><neoplasm/cancer><new approaches><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><new treatment approach><new treatment strategy><novel><novel approaches><novel strategies><novel strategy><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><patient oriented outcomes><programs><prophylactic><receptor><receptor expression><resistant><response><success><tech development><technology development><tenure process><tenure track><thymus derived lymphocyte><trafficking><translational immunology><tumor><tumor microenvironment><viral infection><virus infection><virus-induced disease><xeno-transplant><xeno-transplantation>