# Advancing Treatment Outcomes in Malignant Glioma by Integrating Immunotherapy and Standard of Care using Genetically Engineered Mice that Recapitulate Molecular Feature of Human Glioma

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $45,302

## Abstract

Project Summary/Abstract
In this Administrative Supplement, the candidate, Mr. Vaughn Rogers will generate a checkpoint ligand
PD-L2 conditional knockout mouse strain. During the first funding periods of the parent grant, using
single cell RNA seq, we discovered that both PD-L1 and PD-L2 are predominantly expressed on
immune cells rather than on GBM cancer cells and that our mouse GBM tumors are resistant to anti
PD-1 checkpoint blockade treatment. The hypothesis is that resistance to anti PD-1 immunotherapy is
related to the high levels of PD-L1 and PD-L2 expression in tumor immune cells. PD-L1 and PD-L2 are
ligands of PD-1 and studies in many cancers have shown that high expression of these ligands confers
resistance to anti PD-1 immunotherapy. Here Mr. Rogers is interested in studying the effects of genetic
ablation of PD-L1 and PD-L2. In collaboration with the Boussiotis lab, the Charest lab already obtained
and characterized a conditional PD-L1 knockout strain. Here, Mr. Rogers’ project is to generate a PD-
L2 conditional knockout mouse to study the consequences of inactivating PD-L1 and PD-L2 in innate
intratumoral immune cells on efficacy of anti-PD-1 immunotherapy. In doing so, he will learn the basics
of molecular biology and genome manipulation by generating a Cre/lox conditional knockout mouse
strain for the PD-L2 checkpoint ligand. He will used his knowledge of molecular techniques and learn
new ones to construct a targeting vector, introduce it into mouse embryonic stem (mES) cells, select,
isolate clones, screen clones and generate chimeric animals and germline transmitted knockout stain.
This mouse will then be used in conjunction with immune cell-specific Cre transgenics to selectively
ablate expression of PD- L2 and PD-L1 in specific immune cells and ascertain the consequences on
GBM tumor growth and its response to anti PD-1 checkpoint blockade therapy.

## Key facts

- **NIH application ID:** 10377182
- **Project number:** 3R01CA229784-04S1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** VASSILIKI A BOUSSIOTIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $45,302
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377182

## Citation

> US National Institutes of Health, RePORTER application 10377182, Advancing Treatment Outcomes in Malignant Glioma by Integrating Immunotherapy and Standard of Care using Genetically Engineered Mice that Recapitulate Molecular Feature of Human Glioma (3R01CA229784-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10377182. Licensed CC0.

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