# CHEMOIMMUNO (TOXIN) THERAPY OF METASTATIC PROSTATE CARCI

> **NIH NIH R01** · DUKE UNIVERSITY · 1987 · $82,049

## Abstract

The research plan is designed to evaluate the potential of specific passive
immunotherapy within the context of multimodal therapy to improve
therapeutic modalities for metastatic prostate cancer.  Novel hybrid
immunotoxin monoclonal antibodies (HIT MABs), capable of recognizing
prostate-restricted antigen via one antigen combining site and the toxic
ricin A chain via the remaining antigen combining site, will be evaluated
extensively in vitro for ability to achieve selective prostate carcinoma
cell kill.  The use of primary anti-RAC MABs as immunomodulators to enhance
the cytotoxic impact of HIT-RAC conjugates will be investigated.  More
specifically, anti-RAC MABs to which ricin B chain has been chemically
coupled will be tested for ability to drive the internalization of the
HIT-RAC conjugate and also tested for ability to allow more efficient
transport of RAC within the intracellular membrane compartment; enhanced
transport could be accomplished by recombination of ricin toxic A chain and
binding B chain at the cell surface or within endocytotic vesicles.
Delivery of both A and B ricin subunits would be separate but
site-directed.  Mixtures of prostate-directed MABs reactive with different
molecules and with different epitopes on the same prostate-restricted
molecule, chemically coupled immunotoxins derived from prostate-directed
MABs, and HIT-RAC conjugates will be used to construct a defined synthetic
antiserum in order to enhance both selectivity and magnitude of prostate
carcinoma cell kill.  Immunotherapeutic reagents will be evaluated for
synergy with selected chemotherapeutic drugs to achieve greater prostate
cancer cell kill at a subclinical drug dose.  Those conditions that have
been found optimal for in vitro carcinoma cell kill will be used as
guidelines to achieve cell kill in vivo.  An athymic nude mouse model
system in which metastasis of human prostatic carcinoma cells occurs in a
predictable manner with regard to both time and site of metastasis will be
used to evaluate the in vivo impact of chemoimmunotherapeutic regimes
defined in vitro.  In vivo parameters evaluated will consist of
eradicating, decreasing, or delaying the onset of metastatic disease.

## Key facts

- **NIH application ID:** 3179014
- **Project number:** 5R01CA039690-03
- **Recipient organization:** DUKE UNIVERSITY
- **SAM.gov UEI:** TP7EK8DZV6N5
- **Principal Investigator:** KAREN S WEBB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $82,049
- **Award type:** 5
- **Project period:** 1985-05-01 → 1988-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179014

## Citation

> US National Institutes of Health, RePORTER application 3179014, CHEMOIMMUNO (TOXIN) THERAPY OF METASTATIC PROSTATE CARCI (5R01CA039690-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179014. Licensed CC0.

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