# MACROPHAGE RESISTANCE VS VIRUSES AND TUMORS

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1991 · $173,421

## Abstract

The long term goal of this work is to establish the mechanisms involved
in the generation of diversity in the mononuclear (MP) system, in order to
develop optimum immunotherapy against cancer and viruses through
immunopharmacologic manipulation of MP. The clinical potential of therapy
using MP has not been fully realized, in part due to our lack of
understanding of the origins of the heterogeneity that is extant in this
cell system. We propose two independent experimental approaches to address
the issue of the origins of macrophages (MO) with antitumor activity
against peritoneal and liver tumors selective depletion and stable cell
labelling. The selective cell depletion methods to establish the in vivo
relationships among circulating monocytes, resident peritoneal Mo
(Res89PMO), and resident liver Kupffer cell Mg (Res KC) are: treatment of
mice with 89Sr to "marrow-ectomize" mice and produce monocytopenia, or with
the toxin dichlormethylene diphosphonate encapsulated in liposomes (DMDP-L)
to deplete splenic and liver M0. We will use a stable labelling procedure
with the fluorescent dye, PKH-1, to label Res PMO and KC in vivo. The fate
of the stably labelled Res PMO and KC, in relation, to circulating MP, will
be followed in response to peritoneal or liver tumors in intact mice and
in the mice treated vith 89Sr or DMDP-L. The effect of the
inormomodulators, gamma interferon and BCG, on the host response to tumors
and antitumor efficacy in intact and depleted mice will also be measured.
The peritoneal model will be the multicellular spheroid of the EMT6 mammary
tumor, a model for intracavity immunotherapy of the peritoneal effusions
common after breast-cancer. The liver tumor model will  be intrasplenic
injection of EMT6 or B16 melanoma tumor cells to establish whether
inflammatory or resident M0 are the predominant MP involved in the
natural host response to tumors in intact and depleted mice and which MP
populations are activated for antitumor activity inmmunodulators. These
data will also establish whether these various populations are
independently regulated, and under what conditions immunotherapy can be
effective in severely bone marrow immunosuppressed patients.

## Key facts

- **NIH application ID:** 3173473
- **Project number:** 5R01CA035961-07
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** PAGE S MORAHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $173,421
- **Award type:** 5
- **Project period:** 1983-01-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173473

## Citation

> US National Institutes of Health, RePORTER application 3173473, MACROPHAGE RESISTANCE VS VIRUSES AND TUMORS (5R01CA035961-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173473. Licensed CC0.

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