This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoon, D. S. B. Articles by Morton, D. L. Search for Related Content PubMed PubMed Citation Articles by Hoon, D. S. B. Articles by Morton, D. L.

Suppressor Cell Activity in a Randomized Trial of Patients Receiving Active Specific Immunotherapy with Melanoma Cell Vaccine and Low Dosages of Cyclophosphamide¹

Division of Surgical Oncology, John Wayne Cancer Clinic, Armand Hammer Laboratories, Jonsson Cancer Center [D. S. B. H., L. J. F., A. S. N., D. L. M.], and Division of Nephrology [R. B.], University of California, Los Angeles School of Medicine, Los Angeles, California 90024

Previous studies have shown that melanoma patients develop an immune response to cell surface melanoma-associated antigens. The presence of this antibody response to cell surface antigens has been correlated with a better clinical outcome when melanoma patients are treated with an allogeneic melanoma cell vaccine (MCV) as an active immunotherapy protocol. It was hypothesized that the inability to consistently induce or enhance existing immune responses to melanoma-associated antigens was related to the downregulation by suppressor cells. Patients received treatments of MCV 3 times in a 4-week interval and then every fourth week. The biological response modifier cyclophosphamide (CYP) is an immunomodulator of suppressor T-cell function. In this study we set out to determine whether CYP given prior to MCV could reduce suppressor cell activity during vaccination. In a randomized trial stage II and III melanoma patients (n = 41) were given MCV alone or in conjunction with CYP at dosages of 300, 150, or 75 mg/m². CYP was given 3 days prior to each MCV treatment. Suppressor cell activity in patients was monitored by a concanavalin A suppressor assay using peripheral blood lymphocytes from serial phlebotomies during a 12-week period of treatment. In each trial group there were patients who had major reduction in suppressor cell activity (>50%). Overall, the greatest reduction in suppressor cell activity occurred in patients receiving 300 mg/m² CYP compared to the other CYP dosages or MCV alone. For the first two treatments at all CYP dosages there was a greater number of patients showing reduced suppressor cell activity compared to later treatments. In a comparison of patients receiving MCV alone to MCV + CYP 300 mg/m² phenotypic analysis of lymphocyte subsets showed significant (P = 0.03) reduction in the CD8⁺CD11B⁺ (suppressor) cells of the latter group. These studies suggest that CYP can be used at low dosages in conjunction with MCV to reduce suppressor cell activity.

¹ This study was supported by grant CA 12582 awarded by the National Cancer Institute, United States Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Division of Surgery Oncology, CHS 54–140, UCLA School of Medicine, Los Angeles, CA 90024.

Received 10/17/89. Revised 4/ 3/90.

This article has been cited by other articles:

				A. G. Jarnicki, H. Conroy, C. Brereton, G. Donnelly, D. Toomey, K. Walsh, C. Sweeney, O. Leavy, J. Fletcher, E. C. Lavelle, et al. Attenuating Regulatory T Cell Induction by TLR Agonists through Inhibition of p38 MAPK Signaling in Dendritic Cells Enhances Their Efficacy as Vaccine Adjuvants and Cancer Immunotherapeutics J. Immunol., March 15, 2008; 180(6): 3797 - 3806. [Abstract] [Full Text] [PDF]

				R. A. Wascher, D. L. Morton, C. Kuo, R. M. Elashoff, H.-J. Wang, M. Gerami, and D. S.B. Hoon Molecular Tumor Markers in the Blood: Early Prediction of Disease Outcome in Melanoma Patients Treated With a Melanoma Vaccine J. Clin. Oncol., July 1, 2003; 21(13): 2558 - 2563. [Abstract] [Full Text] [PDF]