# Dissecting intrinsic variability in engineered T Cell immunotherapies > **NIH NIH K08** · STANFORD UNIVERSITY · 2024 · $330,942 ## Abstract PROJECT SUMMARY/ABSTRACT Cancer immunotherapy has revolutionized oncology. Chimeric Antigen Receptor (CAR) T cells in particular have shown dramatic successes in some liquid tumors, with multiple FDA approved products in overlapping heme indications. Yet patient responses to engineered cell therapies are highly variable and unpredictable. Given both the extraordinary cost and extraordinary curative potential of engineered T cell therapies, matching the right cell to the right patient remains a large unmet clinical need. Yet how patient T cells variably respond to the wealth of different potential synthetic genetic alterations remains unexplored. Our long term goal is to develop personalized cellular immunotherapies and the diagnostic tests necessary to nominate the optimal engineered cell for a specific cancer patient. As a first step towards this goal, we will develop scalable pooled screening methodologies to rapidly assay approved and proposed cellular immunotherapy constructs at scale across large numbers of patients (Specific Aim 1). In cohorts of liquid and solid tumor patients, we will dissect the intrinsic variability of patient T cells synthetically engineered with CARs in repetitive stimulation assay models (Specific Aim 2). Finally, we will determine predictive correlates of patient specific engineered T cell function using high dimensional immune cell profiling and patient clinical metadata (Specific Aim 3). We hypothesize that engineered immune cell performance is highly variable and patient specific, and measurements of this variability across cancer patient’s T cells will nominate future predictive diagnostic strategies for personalized cellular immunotherapy choice. In this K08 Mentored Clinical Scientist Research Career Development Award application, the applicant, Dr. Theodore Roth, MD, PhD is a Clinical Pathologist in the Stanford University Department of Pathology. In addition to the enclosed Research Plan, this proposal encompasses a five-year Training Plan to complete his mentored career development with the primary goal of becoming and independent academic physician scientist running a research group devoted to developing personalized cellular immunotherapies. Dr. Roth will undergo training in diagnostic assay development (Training Aim 1), high dimensional immune profiling technologies (Training Aim 2), and successful assumption of research independence (Training Aim 3). Dr. Roth’s remaining mentored training will be overseen by a multidisciplinary group of distinguished physician scientists, including his primary mentor Dr. Ansuman Satpathy and co-mentor Dr. Crystal Mackall, along with a senior Advisory Committee composed of Drs. Ed Engleman, Howard Chang, and David Miklos. Stanford University provides an outstanding environment to complete Dr. Roth’s transition to research independence, with a highly active clinical cell therapy program overseen by his co-mentor, Dr. Crystal Mackall, and vibrant research communities in im... ## Key facts - **NIH application ID:** 10985388 - **Project number:** 1K08CA286740-01A1 - **Recipient organization:** STANFORD UNIVERSITY - **Principal Investigator:** Theodore Lee Roth - **Activity code:** K08 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $330,942 - **Award type:** 1 - **Project period:** 2024-09-01 → 2029-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10985388 ## Citation > US National Institutes of Health, RePORTER application 10985388, Dissecting intrinsic variability in engineered T Cell immunotherapies (1K08CA286740-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10985388. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*