Role of biological response modifiers in immunochemotherapy of solid tumors and retroviral-induced leukemia.

Abstract

Modulation of the immune response by the use of biological response modifiers (BRM) is aimed at amplifying the host resistance against cancer. Studies on inhibition of tumor growth on an in vitro model, in which human breast carcinoma (HBL-100) and human lung carcinoma (H125) cells were used as target tumor cells, confirmed that interferons (IFNs) alpha and beta can amplify the antineoplastic effects of immunochemotherapy by enhancing the cytotoxic activity of effector cells and by antagonizing the immunodepressive effects of radiation or anticancer drugs. Moreover, data obtained from a pilot clinical trial, designed to test the effect of low concentrations of beta-IFN on natural cell-mediated cytotoxicity, pointed out a good correlation between the in vitro and in vivo responsiveness to beta-IFN in cancer patients. The immunomodulating and antiproliferative effects of BRM were also evaluated in a model of viral leukemogenesis in vitro, after infection of cord blood derived mononuclear cells (CB-MNC) with the human leukemic retrovirus HTLV-I. Alpha-and beta-IFN were previously shown to regulate differentially the antiviral competence of recipient CB-MNC, by interfering with viral replication and delaying the emergence of the transformed clone(s). One of the mechanisms of IFN action that contributes to control HTLV-I infection in vitro can be ascribed to their property of partially counteracting the depression of cell-mediated cytotoxicity that follows exposure to HTLV-I. In the light of data previously and herein described, it seems that alpha- and beta-IFN can be considered potential candidates to define combined therapy with antiviral drugs, to control the early stages of retrovirus-associated disease in human pathology.

• Authors: M P Fuggetta, C D'Onofrio, E Bonmassar
• Journal: Annali dell'Istituto superiore di sanita (Ann Ist Super Sanita) Vol. 26 Issue 3-4 Pg. 385-95 ( 1990) ISSN: 0021-2571 [Print] Italy
• PMID: 1708953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Immunologic Factors
• Interferon Type I
• Recombinant Proteins
• Interferons

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Combined Modality Therapy
• Drug Evaluation
• Drug Screening Assays, Antitumor
• Humans
• Immunity, Innate (drug effects)
• Immunologic Factors (pharmacology, therapeutic use)
• Interferon Type I (pharmacology, therapeutic use)
• Interferons (pharmacology, therapeutic use)
• Killer Cells, Natural (drug effects, immunology)
• Leukemia-Lymphoma, Adult T-Cell (drug therapy, therapy)
• Neoplasms (drug therapy, pathology, therapy)
• Recombinant Proteins
• Tumor Cells, Cultured (drug effects)