R01CA304704

CONTROLLABLE SOLID TUMOR IMMUNOTHERAPY BASED ON A WIRELESS THERMOS-ACTIVATOR - ABSTRACT CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY IS A GROUNDBREAKING TREATMENT FOR CANCER, WITH THE POTENTIAL TO ELICIT LONG-LASTING IMMUNE RESPONSES. HOWEVER, ITS APPLICATION IN SOLID TUMORS IS SIGNIFICANTLY LIMITED BY OFF-TUMOR TOXICITIES, WHERE NORMAL TISSUES EXPRESSING SIMILAR ANTIGENS ARE TARGETED, LEADING TO LETHAL SIDE EFFECTS (ON-TARGET OFF-TUMOR TOXICITY, OTOT). THEREFORE, THERE IS AN URGENT NEED FOR HIGH-PRECISION CONTROL OF CAR T CELLS TO CONFINE THEIR ACTIVATION TO LOCAL TUMOR REGIONS. WE PREVIOUSLY DEMONSTRATED THE FEASIBILITY AND SAFETY OF USING MRI-GUIDED FOCUSED ULTRASOUND TO PRECISELY CONTROL CAR-T CELL ACTIVATION THROUGH LOCAL HYPERTHERMIA. DESPITE ITS POTENTIAL, THIS APPROACH HAS NOTABLE LIMITATIONS, INCLUDING RESTRICTED ACCESSIBILITY DUE TO THE NEED FOR SPECIALIZED MRI EQUIPMENT. TO OVERCOME THESE BARRIERS, THIS PROJECT PROPOSES THE DEVELOPMENT OF A WEARABLE PATCH CONTROLLED, WIRELESS THERMO-ACTIVATOR DEVICE THAT ENABLES PRECISE, LOCALIZED CAR-T CELL ACTIVATION AT TUMOR SITES THROUGH CONTROLLED HEAT. THE SYSTEM INCLUDES INJECTABLE, BIODEGRADABLE RECEIVER MICRO-COILS, A WEARABLE OF A FLEXIBLE TX COIL AND A FLEXIBLE METASURFACE. THIS INNOVATIVE APPROACH OFFERS REMOTE THERMAL CONTROL, ACTIVATING THERMO- ACTIVATOR CAR-T (TA-CAR) CELLS WITH HIGH SPATIOTEMPORAL PRECISION, PROVIDING A CONVENIENT, PORTABLE, PATIENT- FRIENDLY ALTERNATIVE TO MRIGFUS. ACCORDINGLY, THREE SPECIFIC AIMS ARE PROPOSED: (1) TO DEVELOP AND OPTIMIZE WIRELESS INJECTABLE THERMO-ACTIVATOR DEVICE, (2) TO TEST WIRELESS THERMO-ACTIVATOR ON ENGINEERED CAR-T CELLS FOR TUMOR CELL KILLING IN VITRO, AND (3) TO EVALUATE THE IN VIVO THERAPEUTIC EFFICACY OF THE WIRELESS THERMO-ACTIVATOR CONTROLLABLE CAR T CELLS IN SOLID TUMOR KILLING. BY PROVIDING A FLEXIBLE, ACCESSIBLE, AND REPEATABLE METHOD FOR CAR-T ACTIVATION, THIS TECHNOLOGY SEEKS TO ENHANCE THE SAFETY AND EFFICACY OF CANCER IMMUNOTHERAPY. WE EXPECT THAT EACH COMPONENT OF OUR APPROACH, WEARABLE CONTROLLED THERMOS-ACTIVATORS, THERMO-CONTROLLABLE CARS, WILL ALLOW OPPORTUNITIES FOR CONTINUOUS EVOLUTION AND ADAPTATION, TARGETING A BROAD RANGE OF SOLID TUMORS AND PRECANCEROUS CONDITIONS. THIS WEARABLE PATCH CONTROLLED THERAPY OFFERS A GROUNDBREAKING ADVANCEMENT IN REMOTE-CONTROLLED IMMUNOTHERAPY AGAINST SOLID TUMORS, HOLDING PROMISE IN TRANSLATIONS TO CLINICAL APPLICATIONS.

University Of Southern California

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

California United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)