# AUGMENTATION OF HUMAN IMMUNITY BY CYCLOPHOSPHAMIDE

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1987 · $176,893

## Abstract

CY can potentiate cellular and antibody-mediated immune responses,
including responses to malignant tumors, in experimental animals.  Under
the auspices of this grant, we have shown that, in patients with advanced
cancer, the administration of CY 300.mg/M2 IV results in:  1) augmentation
of the development of delayed-type hypersensitivity (DTH) and antibody to
the primary antigen, KLH; 2) selective impairment of non-specific
suppressor T cell function of peripheral blood lymphocytes (PBL); and 3)
augmentation of DTH to an autologous melanoma cell vaccine.  The
combination of vaccine with CY pretreatment (3 days before) resulted in
complete regression of metastases in two patients with advanced melanoma.
In this proposal for renewal, we have outlined an experimental plan to
elucidate the mechanism of CY immunopotentiation and to further study its
therapeutic implications.  We will determine whether CY selectively
depletes suppressor or suppressor-inducer T lymphocytes by studying PBL
composition with the newly-developed monoclonal antibodies, anti-Leu 8 and
anti-Leu 15.  We will use PBL from KLH-injected melanoma patients to
determine whether CY inhibits KLH-specific suppressor T cells.  The
approach will be to use the KLH lymphoproliferative response to assay:  1)
suppressor cells present in peripheral blood and 2) suppressors that can be
generated in vitro.  We will also test a novel technique for demonstrating
KLH-specific suppressor cells - the local adoptive transfer of DTH.  We
will further study CY-potentiated immunity to human tumor-restricted
antigens by administering CY followed by an autologous melanoma cell
vaccine.  We will test DTH, autologous mixed lymphocyte-tumor cell (AMLTC)
(proliferative) response, lymphocyte cytotoxicity, and antibody response.
Specificity will be addressed by testing with certain defined
melanoma-associated antigens, e.g., the melanoma-associated proteoglycan.
We will further define the therapeutic efficacy of CY + vaccine by
conducting a phase II trial in melanoma patients with clinically-apparent,
but limited metastatic disease.  Finally, we will determine whether CY
directly inhibits tumor-directed suppressor cells by using the same
strategy that was outlined for KLH-specific suppressors.  Future directions
of this work include:  1) substitution of defined melanoma-restricted
antigens for intact cells in the treatment of grossly metastatic and
sub-clinically metastatic melanoma; 2) treatment of patients with
colorectal cancer by immunization with carcinoembryonic antigen preceded by
CY; and 3) demonstration of melanoma-directed suppressor cells in patients
with stage II disease.

## Key facts

- **NIH application ID:** 3178077
- **Project number:** 5R01CA039248-03
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** DAVID A BERD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $176,893
- **Award type:** 5
- **Project period:** 1985-05-01 → 1988-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178077

## Citation

> US National Institutes of Health, RePORTER application 3178077, AUGMENTATION OF HUMAN IMMUNITY BY CYCLOPHOSPHAMIDE (5R01CA039248-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178077. Licensed CC0.

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