Immunomodulatory Activity of Human Leukocyte Interferon in Cancer Patients: Results Obtained During Pulse Therapy Schedule

Abstract

We evaluated and previously reported the efficacy of alpha-interferon (alpha-IFN) in 84 cancer patients (19). IFN was administered in a pulse fashion given for 3 consecutive days every 4 weeks. We also evaluated the immunomodulatory effect of IFN which constitutes the basis for the current report. Before, during and after courses of IFN treatment, the immune status of the patients was assessed by: (i) circulating immune complexes, (ii) change in lymphocyte type including (a) natural killer (NK) cells, (b) T-cell subsets (suppressor, helper) and (c) HLA-Dr antigen positivity, (iii) myelopoietic differentiation, (iv) macrophage-dependent tumor cytotoxicity with measurements of macrophage-derived growth factor (MDGF), (v) granulocyte functions, (vi) antibody formation against IFN, and (vii) antiproliferative activity of IFN. In addition, LDH, beta-2 microglobulin, and CEA as tumor markers were obtained. High serum or plasma IFN levels were associated with increased activity of T suppressor cells, increased HLA-Dr antigen, and increased NK activity. The increase of these three parameters was directly related to tumor response. In vitro inhibition of tumor cells in tissue culture by IFN culture was predictive of objective tumor response in those patients whose tumor cells were tested. In addition, IFN induced release of MDGF by monocytes. It is apparent that in addition to direct antitumor effect, IFN has multiple modulatory effects on the immune system in man that may aid in tumor control when given in a pulse schedule.

Survival, response and immune effects in a prospectively randomized study of dose strategy for alpha-N1 interferon

“…(Silver et al, 1983), but unexpected on the basis of earlier published results (Golub et al, 1982;Koren et al, 1983;Maluish et al, 1983). However, our findings have more recently gained support from others (Neefe et al, 1986;Medenica & Slack, 1985).…”

Phase II trial of recombinant interferon gamma in refractory undifferentiated carcinoma of the nasopharynx

“…This is in agreement with the results previously reported by Medenica. 28 The 47% objective response rate in advanced gastrointestinal malignancies2' and the 48% response in squamous cell carcinoma of the lung with alpha IFN and CDDP3O are promising preliminary results. A 5FU-folic acid-CDDPalpha IFN combination regimen investigated at the University of Chicago has recently yielded a 70% CR rate in stage IV head and neck cancer.…”

Successful treatment of a patient with postpartum factor VIII inhibitor with recombinant human interferon α 2a

“…The immune response modifier rhIFN is known to suppress specific B-cell function both in vitro and in vivo [Medenica et al, 1985;Sonnenfeld et al, 19841. There is some indication that rhIFN is effective in the treatment of autoimmune disorders such as ITP [Proctor et al, 19881.…”