# A Mouse Model to Assess Long Term Immunotherapy-related Adverse Effects in Children

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $415,499

## Abstract

Cancer immunotherapy has emerged as the most potent and durable treatment for cancers in recent
years. In some solid tumors and hematological malignancies, immunotherapy has become the standard of care,
joining the ranks of conventional treatment such as surgery, chemotherapy, radiation and targeted therapy.
Chimeric antigen receptor – T (CAR-T) therapy has made impressive progress in treatment of pediatric
leukemia. It is highly anticipated that checkpoint inhibitor antibody immunotherapy, such anti-PD-1, anti-PD-L1,
and anti-CTLA4, will be tested in pediatric cancers in clinical trials (some Phase 1 trials are ongoing) . However,
the autoimmune adverse events (irAE) associated with the immunotherapy is quite severe, with greater than
50% of patients developing grade 3 and 4 organ toxicity in adult clinical trials. The report on a Phase 1 trial of
anti-CTLA4 antibody (Ipilimumab) on pediatric cancer patients suggested similar rate of irAE as observed in
adult, although the observation period is too short to identify issues unique for developmental defects unique for
pediatric patients. Therefore, the major challenges in research effort for pediatric cancer immunotherapy are (1)
establishing mouse models to recapitulate irAE, especially the long term irAE unique for pediatric patients; (2)
using mouse models to study the irAE pathogenesis (3) searching new targets to reduce irAE without impeding
anti-tumor efficacy.
 Damage related molecular patterns (DAMPs) play an important role in regulating tissue damages,
antigen presenting cells activation and effector T cell functions. Our previous work demonstrated that CD24-
Siglec signaling pathway suppresses inflammation triggered by DAMPs. We have established a mouse model
that faithfully recapitulates the irAEs in major organs that have been reported in anti-CTLA 4 and anti-
PD-1 immunotherapy clinical trials. Here we propose to characterize the long term irAE in mouse model, and
to examine the role of DAMPs-binding protein CD24 and Siglecs in irAE pathogenesis.

## Key facts

- **NIH application ID:** 9999525
- **Project number:** 5R01CA227671-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Yin Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,499
- **Award type:** 5
- **Project period:** 2018-09-07 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999525

## Citation

> US National Institutes of Health, RePORTER application 9999525, A Mouse Model to Assess Long Term Immunotherapy-related Adverse Effects in Children (5R01CA227671-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999525. Licensed CC0.

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