# SPECIFIC ACTIVE IMMUNOTHERAPY OF HUMAN MELANOMA

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1993 · $251,905

## Abstract

The goal of this proposal is to optimize specific active immunotherapy for
melanoma.  Towards that end, several aspects of the immunology of human
melanoma will be studied, to determine the mechanisms by which some
patients achieve excellent clinical remissions with a therapeutic vaccine
("theraccine").  Theraccine has caused remissions of metastatic melanoma in
20% of patients, with a median response of 17 mo, associated with a rise in
precursors of cytotoxic T lymphocytes (pCTL).  Modifications of theraccine,
such as lysates of 8-methoxypsoralen-sensitized UV light-irradiated cells,
lyophilized lysates, and membrane vesicles, will be assessed by clinical
trials, monitored closely by in vitro immunological assays.  Low-dose
cyclophosphamide and interleukin-2 will be combined with theraccine to try
to increase CTL generation and thus, clinical response rates.  A randomized
Phase III trial in early stage melanoma (lb-lll) will be conducted in an
attempt to eradicate microscopic residual diseases.  To improve and
simplify immunological correlations, additional assays will be compared
with our estimate of the frequency of pCTL, including a proliferation assay
and an assay for "lytic units" of cytotoxicity.  Leukocytes and cytokines
present in regressing lesions will be detected by immunohistochemistry.
The antigens recognized by CTL and the interaction of CTL with melanomas
will be studied in several ways.  Specificity of tumor-infiltrating
lymphocytes (TIL) and CTL from peripheral blood will be analyzed by cold
target competition assays with melanoma lines and histologically different
tumors.  CTL clones will be established, phenotyped for surface markers and
T cell receptor chains, and their specificity examined by direct
cytotoxicity and cold target competition.  CD8+ "classical" CTL and the
broadly reactive (CD4+ only?) CTL found after theraccine treatment will be
compared.  The melanoma peptides recognized by CTL clones will be
identified after Western immunoblotting by proliferation and competition
assays.  Immunogenic peptides will then be sequenced.  The importance of
accessory molecules and major histocompatibility complex alleles,
especially HLA-A2, in the interaction of CTL and melanomas will be studied
by statistical correlations with response, and by sorting or blocking of
cytotoxicity by monoclonal antibodies in vitro.  T cell receptor genes of
cloned CTL from the blood or tumor and of uncloned TIL from regressing
lesions will be examined with antibodies to gene products and by the
polymerase chain reaction.  Limited use of V region genes unique to
melanoma will be identified by subtractive hybridization:  of normal
melanocytes and melanoma cells, and of squamous lung carcinoma and
melanoma.  Immunogenicity of fusion proteins will be tested by
proliferation, competition assays, and cytotoxicity assays with protein-
treated non-melanoma cells.  A preselected combination of highly
immunogenic MAA from cDNA clones will constitute the ulti...

## Key facts

- **NIH application ID:** 3173749
- **Project number:** 5R01CA036233-10
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** Malcolm Stuart Mitchell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $251,905
- **Award type:** 5
- **Project period:** 1988-03-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173749

## Citation

> US National Institutes of Health, RePORTER application 3173749, SPECIFIC ACTIVE IMMUNOTHERAPY OF HUMAN MELANOMA (5R01CA036233-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173749. Licensed CC0.

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