# MOLECULAR MECHANMISM OF LYMPHOCYTE MEDIATED TUMOR LYSIS

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 1990 · $234,801

## Abstract

This proposal represents a continuation of our investigations into the
structure, function and physiological importance of perforin. Perforin is
a component of the cytolytic mechanism of cytotoxic T cells (CTL) and
natural killer (NK) cells. It is contained in cytoplasmic granules that
are secreted during the cytolytic mechanism. Although it has been
established that perforin and granules can play an important in
cytolysis, it is still controversial whether perforin is essential for
killing or even represents a major cytolytic component. Research in this
area has been impeded previously by the unavailability of sensitive
assays for perforin. Our success in the isolation and analysis of cDNA
clones for both murine and human perforin opens new avenues into the
exploration of the crucially important effector mechanisms of CTL and NK.
Accordingly, this continuation application will focus on several new
areas of research intimately related to perforin and cytotoxicity. The
genomic structure of perforin will be investigated and compared to C9.
The regulation of the induced expression of perforin will be studied and
transcriptional or translational control mechanisms uncovered. The cell
biology of the expression of perforin by transfection will be analyzed.
In particular, the influence of granule factors on stability and
cytotoxicity of perforin will be investigated. The requirement for a
secretory apparatus for the mediation of cytotoxicity in transfected
cells will be determined, In anti-sense transfection experiments, it will
be determined whether perforin is essential for the cytolysis of target
cells. In addition to its cytotoxicity, factors that protect cells from
cytotoxicity by perforin (perforin inhibitor) will be isolated and
analyzed. The role of these factors in self protection of  CTL and NK
will be investigated. The perofrin inhibitor will be purified and
characterized. Its structure will be determined by obtaining and
isolating cDNA clones from a human LAK cDNA library. Cumulatively, these
studies will allow an unambiguous assessment of perforin's role in cell
mediated cytotoxicity and the role of perforin inhibitors in killer cell
self protection.

## Key facts

- **NIH application ID:** 3177961
- **Project number:** 5R01CA039201-07
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **SAM.gov UEI:** F8THLJQSAF93
- **Principal Investigator:** ECKHARD R PODACK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $234,801
- **Award type:** 5
- **Project period:** 1988-05-15 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177961

## Citation

> US National Institutes of Health, RePORTER application 3177961, MOLECULAR MECHANMISM OF LYMPHOCYTE MEDIATED TUMOR LYSIS (5R01CA039201-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177961. Licensed CC0.

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