# MOLECULAR TECHNIQUES IN HUMAN CANCER IMMUNOTHERAPY

> **NIH NIH R01** · WISTAR INSTITUTE · 1988 · $102,334

## Abstract

Murine monoclonal antibodies which bind to surface antigens of human tumor
cells provide approaches to the immunotherapy of human cancers by their
ability to target Fc-receptor bearing effector cells and by their indirect
effect on the host's immune system in the induction of anti-idiotypes (Ab2)
and anti-anti-idiotypes (Ab3) which may minimize specific tumor antigens.

We intend to use recombinant DNA techniques to improve the effectiveness of
murine monoclonal antibodies used for immunotherapy.  For this purpose we
shall clone the cDNAs and/or the genes for the light and heavy chains of
hybridomas which produce antibodies with specificity towards human tumor
cells.  The constant regions of the cloned immunoglobulin cDNAs/genes will
be replaced with the corresponding regions of human immunoglobulin genes,
and the fused mouse-human genes will be inserted into animal expression
vectors and introduced into mouse myeloma cells.  The antibodies produced
in this way will be investigated for their ability to interact with the
human immune system and evaluated for use against human cancer.

We have already shown that murine monoclonal antibodies tumoricidal
activity depends on their isotypes.  In the nude mouse system, human
adenocarcinoma growth is inhibited by the IgG3 and IgG2a isotypes, while
IgG1 and IgG2b are ineffective.  The IgG3, IgG2a and IgG1 isotypes are
effective in vitro in ADCC and ADMC, although IgG1 is not tumoricidal in
vivo.  Furthermore, the IgG3 and IgG2a murine isotypes bind preferentially
and with high affinity to human effector cells.  This binding leads to
specific tumor cell destruction in ADMC.  It remains unknown, however, what
mechanisms will be involved in tumor cell destruction with human monoclonal
antibodies of different isotypes.  Since such monoclonal antibodies are at
present not available, we intend to utilize recombinant monoclonal antibody
(rMAb) molecules which contain murine derived V region and human derived C
regions of different isotypes.

To assess whether such monoclonal antibodies of a certain human isotype
possess tumoricidal potential for future immunotherapeutic application in
man, we will (1) identify the FcR's on the effector cell population
reactive with rMAb's of different isotypes; (2) establish which isotypes
are most effective in CDC and ADCC/ADMC against human target (tumor) cells
and (3) to establish their tumoricidal activity in vivo in the nude mouse
system.

## Key facts

- **NIH application ID:** 3179852
- **Project number:** 5R01CA040205-02
- **Recipient organization:** WISTAR INSTITUTE
- **SAM.gov UEI:** DW1XZMGNFBL4
- **Principal Investigator:** PETER J CURTIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $102,334
- **Award type:** 5
- **Project period:** 1986-07-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179852

## Citation

> US National Institutes of Health, RePORTER application 3179852, MOLECULAR TECHNIQUES IN HUMAN CANCER IMMUNOTHERAPY (5R01CA040205-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179852. Licensed CC0.

---

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