# MONOCLONAL ANTIBODIES APPLIED TO TREAT/DIAGNOSE CANCER

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE · 1989 · $175,442

## Abstract

In this renewal application a paired antibody (Ab) tumor targeting
system is being tested in which the first antibody is an anti-tumor
Ab to which we have coupled a hapten, and the second Ab is an
anti-hapten Ab that has been covalently linked to a cytotoxic
drug, a toxin, a radioisotope or a modified lipid on the surface of
liposomes containing a cytotoxic drug.  By attaching multiple
haptenic groups (up to 26 per Ab molecule) to the first antibody,
it is possible to augment the binding of the second Ab-cytotoxic
ligand complex.  Other major advantages of this approach over
conventional targeting protocols include: 1) the ability to purify
antibodies on hapten affinity columns prior to conjugation to the
cytotoxic agent or liposomes and to repurify the cytotoxic-Ab
complexes after coupling, 2) an opportunity to select the second
antibody from over one hundred will-characterized anti-hapten
Abs that are currently available making it possible to determine
the effects of Ab isotope, valence and affinity, 3) use of one set
of second Abs with any other first antibody, and 4) an increase in
the amount of both Ab1 and Ab2 internalized and a decrease in
the amount shed (due to crosslinking of the first Ab bound to the
human lung tumor with the second Ab).  In order to pursue these
studies, we have identified two tumor-associated molecules and
have generated monoclonal Abs specific for these two tumor
markers.  The first molecule is a 160Kd glycoprotein (gp160) that
is present on several different histological types of non-small cell
human lung tumors but is not detectable in lung or most other
normal tissues.  The other tumor marker is the idiotype associated
with a murine B-cell tumor.  In both the human and murine tumor
systems we have demonstrated that Abs are internalized following
binding to the respective tumor markers.  We have also
established that the growth of these tumors in vitro can be
selectively inhibited by radioimmunotherapy, immunotoxins or by
immunospecific cytotoxic drug containing liposomes.  Using
conventional single Ab mediated targeting protocols in vivo, we
have determined that immunospecific liposomes containing a
cytotoxic drug suppress the spread of a primary tumor to another
organ, but often fail to suppress the growth of the established
primary tumor nodules.  In the present proposal we expect to
substantially improve upon current targeting efforts by using the
paired antibody protocol, by increasing access to the tumor using
photodynamic therapy and by eliminating host response to the
targeting antibody by modulating the host's immune response.

## Key facts

- **NIH application ID:** 3171324
- **Project number:** 5R01CA033462-08
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE
- **Principal Investigator:** RICHARD B BANKERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $175,442
- **Award type:** 5
- **Project period:** 1982-09-30 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171324

## Citation

> US National Institutes of Health, RePORTER application 3171324, MONOCLONAL ANTIBODIES APPLIED TO TREAT/DIAGNOSE CANCER (5R01CA033462-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171324. Licensed CC0.

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