# SPECIFIC IMMUNOTHERAPY WITH MONOCLONAL ANTIBODIES

> **NIH NIH R01** · DUKE UNIVERSITY · 1991 · $233,652

## Abstract

Serotherapy provides an appealing approach to eliminate tumor cells that
remain after conventional treatment, particularly in the case of ovarian
carcinoma where monoclonal antibodies or their conjugates can be
administered intraperitoneally to contact residual tumor cells.  Due to
heterogeneity in antigen expression, more than one antibody will be
required to eliminate different subpopulations.  Coordinate expression of
two or more antigens by tumor cells, but not by normal cells should
permit effective serotherapy, provided that coordinate expression is
associated with 'additive or synergistic antitumor activity.  During the
last grant period antigenic targets have been defined on tumor cells that
permit additive or synergistic interactions between different
immunotoxins which contain monoclonal antibodies linked to ricin A chain
(RTA).  Among the targets that permit log additive antitumor activity is
the c-erbB-2 (HER-2/neu) gene product pl85 that is expressed in 87% of
ovarian cancers and overexpressed in 32%.  Using a panel of monoclonal
antibodies, multiple immunochemically and functionally distinct epitopes
have been identified in a linear array on the extracellular domain of
pl85.  Unconjugated antibodies inhibit anchorage independent and
dependent growth of tumor cells that overexpress pl85, an effect that may
relate to modulation of tyrosine kinase activity in the intracellular
domain.  Interestingly, most of the intracellular domain is not required
for pl85 to serve as a target for immunotoxin.  Log additive antitumor
activity has been observed with immunotoxins that bind to different
epitopes of pl85.  Antitumor activity has also been produced by a
combination of immunotoxins directed against pl85 and the epidermal
growth factor receptor (EGFR).  In continued studies we propose to map
epitopes associated with the extracellular domain of pl85 to determine
whether epitopes closest to the cell membrane are the most effective
targets for immunotoxin.  Mechanisms for additive interactions between
unconjugated antibodies will be compared and contrasted with those for
immunotoxins.  Interactions of immunotoxins and ligands reactive with
pl85 and EGFR will be evaluated in clonogenic assays and nude mouse
heterografts.  Synergistic interactions will be sought with an
immunotoxin against a third target p55.  The feasibility of this approach
to serotherapy will be further tested by measuring coexpression of these
antigens on normal and malignant human tissues.

## Key facts

- **NIH application ID:** 3179305
- **Project number:** 2R01CA039930-08
- **Recipient organization:** DUKE UNIVERSITY
- **SAM.gov UEI:** TP7EK8DZV6N5
- **Principal Investigator:** OLIVER MICHAEL COLVIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $233,652
- **Award type:** 2
- **Project period:** 1988-09-30 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179305

## Citation

> US National Institutes of Health, RePORTER application 3179305, SPECIFIC IMMUNOTHERAPY WITH MONOCLONAL ANTIBODIES (2R01CA039930-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179305. Licensed CC0.

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