# MOLECULAR MECHANISMS OF INDUCED IMMUNE CYTOLYSIS

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 1987 · $141,800

## Abstract

Two areas of research both related to killing of human tumor cells by
monoclonal antibody and complement are proposed in this grant application.
One area concentrates on molecular mechanisms of complement-mediated
killing initiated by either a complement-activating monoclonal antibody or
antibody-cobra venom factor (CVF) conjugates.  This project includes the
analysis of cellular defense mechanisms against complement attack and their
modulation by metabolic inhibitors.  In particular, we want to investigate
the role of membrane components in the slow degradation of C3b on
complement-susceptible cells and of the rapid degradation on
complement-resistant cells.  Additional studies will elucidate the role of
antigen expression and internalization of surface-bound complement
components in determining complement susceptibility.  The kinetics of
binding of complement components C4, C5 and C9 will be studied.  We will
investigate the effect of adriamycin to enhance complement susceptibility.
These studies are directed to identify the membrane targets of the
adriamycin action and the mechanism by which adriamycin achieves the
enhanced complement susceptibility.  Based on the observation that
immobilized adriamycin can enhance the complement susceptibility in vitro
we wish to generate antibody conjugates with adriamycin, and to test them
for their in vitro activity, their in vivo pharmacokinetic properties, and
their therapeutic activity in tumor-bearing animals.  We also wish to
identify other complement-enhancing drugs and their mechanisms of action.

The second area of research will focus on covalent conjugates of monoclonal
antibodies with CVF as cytotoxic agents.  Initially, we wish to find a
structural basis for the recently discovered activity differences of CVF
isolated from different Naja naja subspecies.  The investigations on the
effect of heterobifunctional cross-linking reagents on activity and
pharmacokinetic properties of antibody-CVF conjugates will be continued
with new cross-linking reagents.  Another project is to analyze the
localization of antibody-CVF conjugates into tumors.  Subsequently, the
immunotherapeutic effect of antibody-CVF treatment in tumor-bearing animals
will be studied.  Finally, monoclonal antibodies to CVF will be used as a
tool to identify immunogenic epitopes and functional sites on CVF, cobra
C3, and human C3 as an approach to study the structure/function
relationships of these homologous proteins.

## Key facts

- **NIH application ID:** 3173085
- **Project number:** 5R01CA035525-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **SAM.gov UEI:** TF2CMKY1HMX9
- **Principal Investigator:** CARL-WILHELM VOGEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $141,800
- **Award type:** 5
- **Project period:** 1983-07-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173085

## Citation

> US National Institutes of Health, RePORTER application 3173085, MOLECULAR MECHANISMS OF INDUCED IMMUNE CYTOLYSIS (5R01CA035525-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173085. Licensed CC0.

---

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