# TREATMENT OF LEUKEMIA BY ANTIBODY-DIRECTED LIPOSOMES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1991 · $155,457

## Abstract

The overall goal is to facilitate specific intracellular delivery
of cytotoxic agents to human T-cell leukemia using antibody-
directed liposomes.  The approach will begin with in vitro
optimization of endocytosis and cytotoxicity followed by in vivo
studies of efficacy in a nude mouse model.  We have already
demonstrated efficacy of antibody-directed liposomes containing
cytotoxic drug against murine T-cell leukemia in vitro and for
elimination of leukemia cells from bone marrow.  Recent studies
show the ability to selectively inhibit growth in vitro of human
T-leukemia cell lines.

Liposomal drug delivery to the T-leukemia cells will be enhanced
in vitro by:  1) The proper combination of antibodies to provide
optimal cell binding and endocytosis will be selected.  Ligands
which target internalizing receptors such as antibodies against
receptors for transferrin, interleukin 2, low density lipoprotein
and major histocompatibility complex Class 1 will be compared to
surface T-cell antigens such as the CD2, CD3, CD4, CD5, and CD7.
Double targeting with the two different types of antibodies will
also be used as another way to enhance specificity and efficacy.
2) Drug release will be improved through formulation of pH-
sensitive antibody-targeted liposomes which will fuse with the
plasma membrane and release their contents into the cytoplasm when
they encounter the acidic environment of the endosome.  3) New
techniques for trapping drugs using pH gradients will be used to
increase encapsulation efficiency and decrease leakage. Thus
allowing testing of more potent cytotoxic agents.  4) The optimal
liposome formulation will be selected on the results of new
fluorescent assays of binding and endocytosis, electron microscopy
using colloidal gold as a marker of liposomal contents, and by
growth inhibition and limiting dilution assays for efficacy against
the T-leukemia.

The in vivo efficacy will be tested against human T-cell leukemia
lines established in athymic nude mice.  The specificity and
efficacy of the targeted liposomes containing cytotoxic agents for
tumor growth inhibition will be compared to free drug, antibody
alone, and non-specific liposomes.  Toxicity to normal human
hematopoietic progenitor cells will be examined in colony assays
for BFU-E and CFU-C.

Antibody-targeted liposomes, with their attributes of flexibility
in selection of cytotoxic agent, multiple antibody-targeting, and
pharmacokinetic advantages provide a promising new approach to
treatment of T-cell leukemia and lymphoma in adult and pediatric
cancers, as well as to many other disorders involving T-cells, such
as acquired immunodeficiency syndrome, graft versus host disease,
and autoimmune disorders.

## Key facts

- **NIH application ID:** 3178444
- **Project number:** 5R01CA039448-06
- **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:** 1991
- **Award amount:** $155,457
- **Award type:** 5
- **Project period:** 1985-06-01 → 1992-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178444

## Citation

> US National Institutes of Health, RePORTER application 3178444, TREATMENT OF LEUKEMIA BY ANTIBODY-DIRECTED LIPOSOMES (5R01CA039448-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178444. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*