# AUGMENTATION OF HUMAN IMMUNITY BY CYCLOPHOSPHAMIDE

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1992 · $219,108

## Abstract

Pretreatment of animals with cyclophosphamide (CY) can
augment cell-mediate immunity to tumor-associated antigens.
This immunopotentiating effect is probably caused by selective
toxicity for T lymphocyte-mediated suppressor activity.  We have
shown that pretreatment of patients with advanced cancer with
CY, either 1000 or 300 mg/M2, significantly augmented the
development of delayed-type hypersensitivity (DTH) to the
primary antigen, keyhole limpet hemocyanin (KLH).  Furthermore,
we observed that administration of CY 3 days prior to injection of
an autologous tumor vaccine resulted in the acquisition of DTH to
the autologous tumor cells in a group of patients with metastatic
melanoma who did not become immunized without CY.  To date,
treatment with CY + vaccine has resulted in clinically important
regression of metastases in 4/33 patients.  Studies with peripheral
blood lymphocytes (PBL) from these patients indicate that CY
inhibits the generation of T suppressor cells, possibly by toxicity
for a suppressor-inducer cell with the phenotype, CD4+,2H4+.  We
now propose to continue and extend these studies:  Specific aim 1)
is to identify and characterize melanoma antigen-responsive
suppressor T cells.  We will exploit a recently developed method
to test the effect of putative suppressors on in vitro responses to
melanoma cells and an established technique utilizing suppressors
elicited by melanoma cells but tested in a mitogen-activated
indicator system.  Specific aim 2) is to determine whether
heterogeneity of expression of melanoma-associated antigens is
an important limitation to the effectiveness of active
immunotherapy and whether it can circumvented by therapeutic
modification.  Specific aim 3) is test the hypothesis that the
response to tumor antigens can be augmented by immunizing with
trinitrophenol-conjugated tumor cells in the absence of
suppression, thereby inducing a population of amplified helper
cells or possibly contrasuppressor cells.  Finally, Specific aim 4) is
an attempt to take advantage of the concept that tolerance to
self-antigens, and perhaps tumor antigens as well, is HLA-
restricted and can be reversed by presenting those antigens in the
context of foreign HLA products, i.e., on allogeneic cells.  We
expect these studies to lead to more effective immunotherapy of
human melanoma.

## Key facts

- **NIH application ID:** 3178081
- **Project number:** 5R01CA039248-08
- **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:** 1992
- **Award amount:** $219,108
- **Award type:** 5
- **Project period:** 1985-05-01 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178081

## Citation

> US National Institutes of Health, RePORTER application 3178081, AUGMENTATION OF HUMAN IMMUNITY BY CYCLOPHOSPHAMIDE (5R01CA039248-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178081. Licensed CC0.

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