# TUMOR CYTOLYSIS BY MONONUCLEAR LEUKOCYTES

> **NIH NIH R01** · NEW YORK UNIVERSITY · 1987 · $161,045

## Abstract

Studies will be designed to elucidate how unsensitized mononuclear
leukocytes obtained from the peripheral blood of healthy individuals
recognize and kill tumor cells.  The majority of the studies will be
carried out with large granular lymphocytes (LGL) or a phenotypically
defined subset, natural killer (NK) cells.  Some experiments will utilize
monocytes.  So far, the "recognition" component of this phenomenon has been
more resistant to analysis than the lysis step.  Recognition involves
overlapping concepts:  Effectors may have to preferentially seek out their
targets; next, they must adhere to the targets because cytolysis is known
to be dependent on conjugation.  Moreover, conjugation alone does not
necessarily result in lysis.  Thus, three aspects of "recognition" will be
addressed.  In order to learn how sensitive tumor cells differ from
resistant targets, we shall carry out parallel studies on various target
cell panels:  1) a panel of melanoma cell lines, which are known to be
either NK sensitive (NKs) or NK resistant (NKr), 2) fetal and transformed
fibroblasts (NKs) and normal adult fibroblasts (NKr), 3) cell lines which
are NK(s) like K562, U937 and HL60 and which can be induced to
differentiate when they become NK(r), and 4) cells which are NK(r) but can
be rendered NK(s) in vitro, e.g., by treatment with phorbols.  Comparable
target cells and their isolated membranes will be subjected to biochemical,
histochemical, immunochemical, ultrastructural and freeze-fracture analyses
to pinpoint the target structure(s) responsible for NK cell recognition.
Among candidate molecules to be studied are:  fibronectin, laminin,
transferrin, and hemopoxin, as well as the receptors for these proteins.
Isolated receptors which may constitute the "recognition" units on the
target membrane and which may be "shed" into the microenvironment of tumor
cells, will also be used in chemotaxis assays.  A variety of well defined
tumor cell antigens to which monoclonal antibodies are available will be
used similarly.  In addition, we hope to determine on the ultrastructural
level, by means of freeze-fracture and "label-fracture" techniques, where
in the membrane these structures are located and whether they are lost,
translocated or "covered up" when there is a change from NK(s) to NK(r) or
vice versa.  An understanding of the mechanism of spontaneous tumor
cytolysis is obviously necessary before modulation of effector or target
cells aimed at a therpeutic intervention of neoplastic disease in man can
be envisioned.

## Key facts

- **NIH application ID:** 3172067
- **Project number:** 2R01CA034378-04A1
- **Recipient organization:** NEW YORK UNIVERSITY
- **SAM.gov UEI:** NX9PXMKW5KW8
- **Principal Investigator:** DOROTHEA ZUCKER-FRANKLIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $161,045
- **Award type:** 2
- **Project period:** 1983-05-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172067

## Citation

> US National Institutes of Health, RePORTER application 3172067, TUMOR CYTOLYSIS BY MONONUCLEAR LEUKOCYTES (2R01CA034378-04A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172067. Licensed CC0.

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