# SPECIFIC IMMUNOTHERAPY WITH MONOCLONAL ANTIBODIES

> **NIH NIH R01** · DUKE UNIVERSITY · 1989 · $158,278

## Abstract

With the development of the monoclonal technology, serotherapy of
cancer can  finally be evaluated critically in the clinic.  The
major problems encountered to date include the therapeutic potency
of monoclonal antibodies and the phenotypic heterogeneity of tumor
cell targets.  To increase the potency of monoclonal antibodies,
conjugates have been prepared with drugs, radionuclides or plant
toxins.  One potential advantage of toxin conjugates is their great
specificity, killing only those cells which bind and take up the
immunotoxin.  One potential limitation is the presence of cells
within a tumor which fail to bind the immunoconjugate or fail to
take up and translocate the toxin.  During the last 4 years we have
studied methods for overcoming the phenotypic heterogeneity among
tumor cells to achieve complete and selective elimination of B
lymphoma, T lymphoma and breast cancer cells from human bone
marrow.  In the course of these studies, a synergistic interaction
has been observed between immunotoxins which bind to two distinct
cell surface proteins expressed by >90% of breast and ovarian
carcinomas.  In continued studies, we propose to define mechanisms
which contribute to this synergistic antitumor activity.  We will
test the hypothesis that synergistic interactions of immunotoxins
depend upon different patterns of expression, trafficking or
cooperativity of different target antigens and that these
characteristics, in turn, depend upon the structure of the antigens
and their interaction with membranes before and after immunotoxin
binding.  Factors will be studied which regulate expression of
antigens know to make effective targets for immunotoxins.  New
antigenic targets will be sought based upon the outcome of these
studies.  Two of the most promising areas for clinical application
of these observations will be explored.  Immunotoxins which exert
synergistic antitumor activity will be used to eliminate breast
cancer cells from human bone marrow, facilitating autologous bone
marrow transplantation in this disease.  Preclinical studies will
be undertaken in a nude mouse heterograft model for epithelial
ovarian cancer to determine whether synergy can be demonstrated in
vivo as well as in cell culture.

## Key facts

- **NIH application ID:** 3179310
- **Project number:** 5R01CA039930-06
- **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:** 1989
- **Award amount:** $158,278
- **Award type:** 5
- **Project period:** 1984-10-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179310

## Citation

> US National Institutes of Health, RePORTER application 3179310, SPECIFIC IMMUNOTHERAPY WITH MONOCLONAL ANTIBODIES (5R01CA039930-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179310. Licensed CC0.

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