# PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCC

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1993 · $251,936

## Abstract

We have been investigating the antigenic characteristics of primary human
hepatocellular carcinoma (HCC) cells.  Employing monoclonal antibodies
(MAbs) important cell surface antigenic changes associated with transformed
hepatocytes have been identified.  We will pursue investigations that
explore antigenic differences displayed on the cell surface during
hepatocyte transformation to the malignant phenotype.  We have now defined
10 antigens of interest (XF-4, XF-8, AF-5, AF-20, AF-10, SF-25, SF-17,
SF-32, SF-90 and FB-50).  We plan to:  1) examine antigen expression in
various liver diseases such as adenomas, cirrhosis, regenerating nodules,
and chronic active hepatitis compared to HCC and other normal tissues.  2)
determine some of the biochemical and physical properties of these
antigens.  3) perform cDNA cloning in lambda GT10 as well as lambda GT11
and CDM8 expression vectors.  4) obtain primary sequence information on the
cDNAs of interest.  5) study gene expression at the protein and mRNA level
in HCC and adjacent uninvolved liver, in various liver diseases, other
tumors and normal tissues.  Since MAbs XF-8, AF-20 and SF-25 may have
sufficient sensitivity and tissue specificity to be strongly considered as
immunotargeting agents in man, we plan to perform experiments with
radiolabeled, drug and toxin antibody conjugates to determine their effects
either alone or in combination on the growth rate of HCCs in a new animal
model system.  These tumors produce both hepatitis B surface antigen
(HBsAG) and alphafetoprotein (AFP) which will be used as another
independent marker of tumor cell growth and viability.  The cDNA of some of
these antigens have been cloned.  These investigations have led to the
development of novel reagents for nuclear imaging and potential
immunotherapy.  In HCC we have observed the existence of low level
hepatitis B virus (HBV) or variant viral infection.  These agents need to
be characterized at the molecular level.  We plan to perform studies on
HBsAG negative HCC patients with and without serologic markers of past HBV
infection.  From serum we will first capture on a solid phase support, HBV
or variants with different high affinity monoclonal anti-HBsAG antibodies
that recognize all known subtypes of HBV.  We will employ the polymerase
chain reaction (PCR) to subsequently detect and amplify HBV or variant DNA
sequences in serum, lymphocytes, tumor tissue and adjacent uninvolved
liver.  We expect that the studies outlined in the present application will
help to define the molecular events associated with human hepatocyte
transformation and will result in novel reagents for immunodiagnosis and
therapy.

## Key facts

- **NIH application ID:** 3173313
- **Project number:** 5R01CA035711-10
- **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:** 1993
- **Award amount:** $251,936
- **Award type:** 5
- **Project period:** 1983-07-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173313

## Citation

> US National Institutes of Health, RePORTER application 3173313, PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCC (5R01CA035711-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173313. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
