R01CA271682

Validation of a Novel 3D Culture Platform for TNBC Treatment Selection - Project Summary

The goal of this academic [Houston Methodist Research Institute (HMRI) and MD Anderson Cancer Center (MDACC)] and industrial (EMPIRI) collaborative project is to validate a novel, functional cancer diagnostic assay for clinical translation to improve and personalize the care of triple-negative breast cancer (TNBC) patients.

The study will validate a novel 3D tumor tissue culture method (E-SLICES) invented by MPI Kyuson Yun (HMRI) and licensed to EMPIRI, Inc., a biotech startup co-founded by Dr. Yun and Dave Gallup (MPI). Together with Dr. Naoto Ueno (MPI, MDACC), a renowned physician-scientist specializing in TNBC research and patient care, the team will validate the predictive accuracy of E-SLICES for individual TNBC patient responses to recently approved chemoimmunotherapy for early TNBC patient care.

The need for personalized medicine in oncology is widely accepted but translating this important concept into clinical practice has been challenging. Currently, the dominant platform for precision medicine utilizes genomics/sequencing-based assays to measure the expression and/or mutational profiles and then infer responses to targeted therapies; however, this approach benefits <10% of patients with profiled tumors.

Recognizing the inherent limitations of these inference-based methods, functional assays (e.g., organoids, PDX models) have been developed, but these approaches have numerous limitations including high cost and time required to establish the models, low "take rates," and destruction of the native tumor microenvironment (TME).

To overcome these challenges, EMPIRI developed a novel 3D ex vivo tumor culture method (E-SLICES) that enables rapid, personalized drug sensitivity testing in intact patient tumor tissues. E-SLICES retain the native TME and tissue architecture and are cultured in serum-free defined media, overcoming the limitations of other approaches. In addition, E-SLICES can be generated from any solid tumor and used for testing responses to chemotherapy, targeted therapy, and immunotherapy.

Importantly, E-SLICE accuracy has been validated in a clinical setting for metastatic colorectal cancer to accurately predict individual patient treatment responses and detect inter-patient differences to the same treatments in 4-12 days, paving the way for near evidence-based personalized treatment selections.

The team will:
(I) Determine whether E-SLICES predict patient responses to SOC NAC: doxorubicin (Adriamycin) plus cyclophosphamide) in a retrospective study,
(II) Measure chemoimmunotherapy (pembrolizumab plus paclitaxel + carboplatin) responses in humanized PDX slices from known responders and non-responders; and
(III) Evaluate the clinical utility of E-SLICES in predicting TNBC patient responses to newly approved standard of care chemoimmunotherapy in a prospective study.

Successful completion of this project will provide the necessary data to apply E-SLICES as the first functional cancer diagnostic test specifically designed to inform TNBC patient care.

Methodist Hospital

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]

Houston, Texas 77030 United States

Single Zip Code

Academic-Industrial Partnerships for Translation of Technologies for Diagnosis and Treatment (R01 - Clinical Trial Not Allowed) (PAR-21-166)

Amendment Since initial award the total obligations have increased 370% from $644,226 to $3,027,149.