# PATHOGENENSIS IMMUNODIAGNOSIS AND THERAPY OF CARCINCOMA

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1988 · $174,616

## Abstract

Human hepatocellular carcinoma (HCC) represents a major
worldwide disease and is often associated with chronic hepatitis B
virus (HBV) infection.  In this proposal we will focus on three
major aspects of HCC:  1) viral pathogenesis, 2) techniques for
immunodiagnosis, and 3) development of antibodyconjugates for
immunotherapy.  In this regard we have developed a library of
high affinity monoclonal antibodies directed against distinct and
separate determinants present on human hepatoma cells.  Such
reagents will be used to develop in vitro and in vivo reagents for
immunodiagnosis.  Indeed, one such antibody, namely P215457
recognizes a 50 kd (P50) cell surface protein present on both
human and rat hepatoma cell lines as well as human hepatoma
tissue; this antigen appears relatively restricted to transformed
hepatocytes and was not detected in normal human tissues.  The
Fab fragment of P215457 has been prepared and radiolabeled with
(131I).  Based on in vivo nuclear imaging studies in a nude mouse
system, we now believe that this reagent is suitable for detection
of HCC in man.  The physical and molecular characteristics of
P50 will be studied in greater detail.  It is noteworthy that a new
library of 124 monoclonal antibodies have neen produced to
affinity purified P50.  We now plan to search for this antigen and
other similar antigens in serum of patients with multisite
monoclonal radioimmunoassays (M-RIAs).  Therefore it is our goal
to provide immunodiagnostic techniques which will detect HCC at
an early stage when the tumors may be surgically resectable.
Recent in vitro and in vivo investigations suggest that these
monoclonal antibodies may have value in the treatment of HCC.
We will extend and consolidate these findings and covalently link
the monoclonal antibodies to cytotoxic agents such as adrimycin
and isotopes such as (131I).  Finally, our recent studies suggest the
presence of HBV or HBV "variants" in some seronegative (by
conventional assays) patients with HCC.  Thus we will further
explore the role of HBV in the development of HCC using a
recently developed second generation antiHBs RIA.  The assay is
capable of detecting as little as 15 pg/ml of HBsAG-associated
epitopes in serum.  The studies will also include affintiy
purification and structural analysis of antigens by a newly
developed technique designated signature analysis.  We are
optimistic that such studies will provide new information on the
viral pathogenesis of HCC.

## Key facts

- **NIH application ID:** 3173309
- **Project number:** 5R01CA035711-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** Jack R Wands
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $174,616
- **Award type:** 5
- **Project period:** 1983-07-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173309

## Citation

> US National Institutes of Health, RePORTER application 3173309, PATHOGENENSIS IMMUNODIAGNOSIS AND THERAPY OF CARCINCOMA (5R01CA035711-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173309. Licensed CC0.

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