Cytotoxic In vitro function in patients with metastatic renal cell carcinoma before and after alpha‐2b‐interferon therapy effects of activation with recombinant interleukin‐2

• Published in: Cancer Vol. 69; no. 10; pp. 2525 - 2531
• Main Authors: Feruglio, Cristina, Zambello, Renato, Trentin, Livio, Bulian, Pietro, Franceschi, Tiziano, Cetto, Gian Luigi, Semenzato, Gianpietro
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15.05.1992; Wiley-Liss
• Subjects: Adult; Aged; Antigens, Neoplasm - drug effects; Antigens, Surface - drug effects; Biological and medical sciences; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - secondary; Carcinoma, Renal Cell - therapy; Cytotoxicity, Immunologic - drug effects; Female; Humans; Immunomodulators; In Vitro Techniques; Interferon alpha-2; Interferon-alpha - therapeutic use; Interleukin-2 - pharmacology; Kidney Neoplasms - immunology; Kidney Neoplasms - therapy; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Recombinant Proteins - pharmacology; Human; Urinary system disease; Alpha interferon; Cytotoxicity; Renal disease; Metastasis; Malignant tumor; In vitro; Biological activity; Immunomodulator; Chemotherapy; Treatment; Interleukin 2
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19920515)69:10<2525::AID-CNCR2820691023>3.0.CO;2-D

In this study the characteristics of the cytotoxic function in a series of patients with metastatic renal cell carcinoma (RCC) were analyzed and the possibility of modulating this capacity in vitro with the use of biologic response modifiers (BRM) such as alpha‐interferon (α‐IFN) and recombinant interleukin‐2 (rIL‐2) was verified, with the ultimate goal of providing a rationale for a therapeutic approach to this disease with these molecules. Peripheral blood mononuclear cells (PBMC) of patients with advanced RCC were tested for natural killer (NK) and lym‐phokine‐activated killer (LAK) activity both before and after α‐IFN therapy. In addition, surface markers of un‐stimulated and stimulated cells were analyzed and in vitro assays were performed to determine the proliferative capacity in response to the stimulus with rIL‐2. During an evaluation before treatment, defective NK activity was observed that could be corrected by incubating the cells with rIL‐2. In these subjects, LAK cells could be consistently generated after PBMC were activated with this cytokine in vitro. No changes in NK and LAK activity were found after α‐IFN therapy. In contrast, treatment with α‐IFN affected the proliferative response of PBMC to rIL‐2, and a significant decrease in this in vitro capacity was observed during follow‐up. The ability to restore NK activity and obtain an adequate LAK cytotoxicity from the PBMC of patients with RCC supports a therapeutic approach with BRM. However, the fact that this type of treatment affects the proliferative response of PBMC to rIL‐2 must be considered when clinical trials are designed for patients with RCC.