# MECHANISM OF THE NK LETHAL HIT IN PROGRAMMED TUMOR CELLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1988 · $151,425

## Abstract

Natural killer cells are a subpopulation of Fc receptor positive,
nonadherent, nonphagocytic cytotoxic effector cells present in
the large granular lymphocyte fraction of human peripheral blood
lyumphocytes which can recognize and lyse tumor cells, virally
infected cells, fetal fibroblast, thymus cells and B cell lines and
may be involved in auto-regulation of at least thymocytes, bone
marrow stems cells, epithelial cells, and terminally differentiated
B cells.  The long term objective of this study is to determine the
molecular events which occur during the lethal hit stage of
natural killer cell-mediated cytotoxicity (NK CMC).  The
objective of this present proposal is to determine the relevance of
lytic factors secreted from NK cells to events occurring during
the lethal hit stage of direct NK CMC.  Since it has been shown
that the activity of natural killer cell-derived cytolytic factor
(NKCF) is closely correlated to that which occurs during lysis of
programmed target cells, this study will examine in detail, the
role that these factors may play in direct NK CMC.  This shall be
accomplished by separating these factors and preparing
monoclonal antibodies by screening for antibodies that inhibit
NKCF lytic activity.  These anti-NKCF antibodies will be used to
determine the fate of target cell associated NKCF and where in
the NKCF reaction sequence that antibodies to NKCF inhibit
NKCF-mediated lysis.  The role of NKCF in direct NK CMC will
be determined by interacting labeled anti-NKCF antibodies with
resting and activated NK cells to determine its intracellular
location and to kinetically determine is location in both the NK
cell and the target cell during the stages of NK CMC.  These
studies in conjunction with kinetic studies will allow us to
determine where in the NK reaction sequence that antibodies to
NKCF inhibit NK CMC and killer cell independent lysis (KCIL).
These results should determine whether NKCF is a lytic factor
that is involved in the terminal lethal hit phase of the NK lytic
mechanism.

## Key facts

- **NIH application ID:** 3174994
- **Project number:** 5R01CA037205-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** Stephan R. Targan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $151,425
- **Award type:** 5
- **Project period:** 1984-03-15 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174994

## Citation

> US National Institutes of Health, RePORTER application 3174994, MECHANISM OF THE NK LETHAL HIT IN PROGRAMMED TUMOR CELLS (5R01CA037205-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174994. Licensed CC0.

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