# Decoupling acute toxicities and antitumor efficacy in adoptive cell therapy

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $600,313

## Abstract

Project Summary
Adoptive cell therapy (ACT) with chimeric antigen receptor (CAR) T cells has demonstrated impressive
response rates in B cell malignancies, but ACT has not mediated sustained responses in solid tumors. CD19
CAR T cell therapy has reached up to 80% response rate in the clinic; however, the main side effects are
cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which
occur in 37–83% and about 25-35% of patients, respectively. Furthermore, one of the major obstacles in ACT
is the heterogeneity of targeted antigens and relapse due to antigen escape. Recently, we screened a cohort
of 16 FDA-approved anti-inflammatory drugs and identified clofazimine (CLF) as the top candidate for its
desired bifunctional effect for anti-CRS/ICANS and anti-antigen escape roles. Aim 1 will determine the role of
CLF in reducing macrophage-derived ROS to curtail CRS/ICANS. Aim 2 will determine the role of CLF in
driving dsRNA/dsDNA signals in macrophages for the eradication of tumors. We expect this study to
demonstrate the ability of CLF in potentiating the anti-antigen escape capacity in ACT, curbing intractable
CRS, and may also fill a desperate clinical need to improve the dismal patient survival with ICANS. This
strategy of repurposing the clinically approved CLF may hold great promise to overcome a critical obstacle in
realizing the full potential of ACT with CAR-T cells. This translationally relevant work could then lay the
foundation for future clinical trials.

## Key facts

- **NIH application ID:** 10850196
- **Project number:** 1R01CA288403-01
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Yong Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $600,313
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850196

## Citation

> US National Institutes of Health, RePORTER application 10850196, Decoupling acute toxicities and antitumor efficacy in adoptive cell therapy (1R01CA288403-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10850196. Licensed CC0.

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