# TREATMENT OF BONE MARROW BY ANTIBODY-DIRECTED LIPOSOMES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1987 · $113,608

## Abstract

The purpose of this investigation is to use antibody-directed liposomes
containing cytotoxic agents to achieve specific in vitro destruction of
leukemia cells in murine bone marrow prior to bone marrow transplantation.
The model system will be the murine T-cell leukemia, AKR/J SL2, which can
be implanted in congenic AKR/Cu mice, who differ only at the Thy 1
antigen.  We have already shown effective and specific in vitro cell growth
inhibition of SL2 leukemia cells by methotrexate-Gamma-aspartate
encapsulated in liposomes conjugated with anti-Thy 1.1 antibody.  Drug
encapsulated in staphylococcal protein A-conjugated-liposomes
(SPA-liposomes) is even more effective against the SL2 cells.  The
SPA-liposomes are 50-fold more effective against cells that have been
pre-incubated with anti-Thy 1.1 than against SL2 cells incubated with
non-specific antibody, and 144-fold more effective than free drug.  Cell
growth assays will be used to determine the optimal SPA-liposomes with
regard to lipid composition, choice of drug, and choice of antibody or
combinations of antibodies.  The liposome efficacy will then be confirmed
in a colony assay.  The SPA-liposomes will be tested both in vitro and in
vivo on mixtures of SL2 tumor cells seeded into congenic AKR/Cu murine bone
marrow.  The maximum number of cells that can be eradicated will be
determined in a colony assay.  Finally, lethally irradiated mice will
receive an infusion of treated bone marrow to determine the effect of the
drug-containing antibody-directed SPA-liposomes on hematologic
reconstitution and efficacy for elimination of leukemia.  This
investigation will provide a new strategy for eradication of tumor cells
prior to autologous bone marrow transplant in patients who have leukemia.
Antibody-directed liposomes offer the advantages of more flexibility in
selection of cytotoxic agent, the possibility of multiple antibody
targeting and potential utility in post-transplant adjuvant therapy.

## Key facts

- **NIH application ID:** 3178442
- **Project number:** 5R01CA039448-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** KATHERINE Kurshan MATTHAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $113,608
- **Award type:** 5
- **Project period:** 1985-06-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178442

## Citation

> US National Institutes of Health, RePORTER application 3178442, TREATMENT OF BONE MARROW BY ANTIBODY-DIRECTED LIPOSOMES (5R01CA039448-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178442. Licensed CC0.

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