# Protective Role of Nonclassical Monocytes in Immunotherapies for Solid Cancers

> **NIH NIH U01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $448,200

## Abstract

Nonclassical monocytes (identified as CD14dimCD16+ in humans) exhibit a unique ability to `patrol' or survey
the luminal side of the vascular endothelium both at steady state and during inflammation. Nonclassical
monocytes function in circulation to aid in removing pathogens and debris from the vasculature. We recently
found that nonclassical monocytes function in the vasculature to prevent tumor metastasis by orchestrating
the killing and clearance of metastasizing tumor cells. The anti-tumor immune potential of nonclassical
patrolling monocytes is in contrast to the growing evidence for pro-tumorigenic and pro-metastatic functions
of myeloid cells in many tumor types. In the current proposal, we hypothesize that nonclassical monocytes
function in an anti-tumoral manner to support CAR T cell expansion and efficacy in patients with solid
tumors. Thus, one major goal of our proposal is to determine whether monocyte therapy using anti-tumoral
nonclassical monocytes in combination with existing CAR T immunotherapy would improve efficacy. We will
use mass cytometry to study monocyte subsets in cancer patients to identify new markers that will help
readily determine how successful a proposed immunotherapy may be for patients. Aim 1 will identify unique
markers of nonclassical monocytes in multiply relapsed sarcoma patients versus healthy subjects using
mass cytometry. Aim 1 will be performed using banked samples from the existing GD2 CAR T trial at the
NIH Clinical Center. Aim 2 will test the hypothesis that nonclassical monocytes play a functional role in
promoting anti-tumor immunity when used in combination with immunotherapy for solid tumor metastasis.
Aim 2 will use both xenografted humanized mouse and syngeneic mouse tumor models. Aim 3 will study
the safety and preliminary efficacy of CAR T cell immunotherapy in combination with nonclassical monocyte
cell therapy for patients with multiple relapsed, metastatic or progressive pediatric solid tumors. In Aim 3, we
will initiate a second generation GD2 CAR T cell trial for multiply relapsed patients with osteosarcoma and
neuroblastoma. Given the potential anti-tumor efficacy of patrolling monocytes we plan to initiate an early
phase clinical trial delivering nonclassical monocytes alone and in combination with CAR T cell therapy as
part of this trial. There are 3 investigators in this project: one extramural, one intramural at NCI, and one at
the NIH Clinical Center. From the results of this proposal, we will achieve significant insight into the roles of
various myeloid cell subpopulations on promoting and inhibiting the anti-tumoral responses of CAR T cell
therapies for solid tumors. We are uniquely poised as a research team to directly address the role of
monocytes and other myeloid cells in interacting with CAR T cells in human patients. The findings of our
research team will significantly advance the knowledge that will lead to effective CAR T cell therapy for solid
tumors. As similar interacti...

## Key facts

- **NIH application ID:** 9899213
- **Project number:** 5U01CA224766-03
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Catherine C Hedrick
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,200
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899213

## Citation

> US National Institutes of Health, RePORTER application 9899213, Protective Role of Nonclassical Monocytes in Immunotherapies for Solid Cancers (5U01CA224766-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899213. Licensed CC0.

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