# Core 1: Mouse Model and Tissue Biobank Core

> **NIH NIH U54** · INSTITUTE FOR SYSTEMS BIOLOGY · 2022 · $322,871

## Abstract

Murine and Clinical Tumors (MCT) Core services. Project Summary
The simultaneous combination of anti-PD-L1 with BRAFV600MUT and MEK inhibitors (so-called “triplet” therapy),
in early clinical data, appears beneficial and has recently been approved for patients with BRAFV600MUT melanoma
(13). This is first mutation-immune co-targeted therapy to be approved, but the data on this triplet appear mixed,
with other trials not meeting key endpoints (14), suggesting that simultaneous combination is not optimal.
Importantly, retrospective clinical data analysis and in vivo therapeutic modeling using syngeneic models of
murine melanoma showed that a regimen of anti-PD-1/L1 (± anti-CTLA-4) lead-in before MAPKi combination
augments the efficacy of triplet therapy by enhancing MAPKi durability (and overcoming innate resistance to
immune checkpoint blockade) (12). Thus, the realization that immune factors drive resistance to MAPKi therapy
opens the door to immune-based strategies, such as adoptive cell therapy (ACT) (Project 1, Aim 3), as
combinatorial agents to prevent MAPKi resistance.
Building on this recent progress, this Murine and Clinical Tumors (MCT) Core will offer Projects 1 and 2 model
and clinical tumors to obtain multi-scale (spatiotemporal) profiles of the tumor immune microenvironment (TIME)
early and late on single-agent (MAPKi or anti-PD-1/L1) therapy (Project 1, Aim 1). These “early” data will provide
inputs to the agent-based models (ABMs) being developed in Project 1, Aim 2, and “late” data will help validate
predictions. Profiles from more successful combination strategies will be compared against less successful
combination strategies to teach the ABM on optimized TMEs. This core will also offer clinical tissues for
translational validation (Project 1, Aim 4) and tumor models to test predicted novel combination therapies
(Project 2, Aim 3).

## Key facts

- **NIH application ID:** 10526106
- **Project number:** 1U54CA274509-01
- **Recipient organization:** INSTITUTE FOR SYSTEMS BIOLOGY
- **Principal Investigator:** ROGER S LO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $322,871
- **Award type:** 1
- **Project period:** 2022-09-22 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526106

## Citation

> US National Institutes of Health, RePORTER application 10526106, Core 1: Mouse Model and Tissue Biobank Core (1U54CA274509-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10526106. Licensed CC0.

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