Sequential treatment of patients with advanced renal cell carcinoma with autologous tumor vaccine and subcutaneous administration of recombinant interleukin-2 and interferon ?2b

Abstract

Thirty patients with advanced renal cell carcinoma (RCC), 23 of whom had distant metastases in at least one organ, were entered after nephrectomy into a protocol involving vaccination with Newcastle disease virus (NDV)-modified autologous tumour material, with a subsequent induction week and repetitive bi-weekly cycles of interleukin-2 (rIL-2) and interferon ~2b /rlFN-a~b at a lower s.c. dose (1.5 million Cetus units m -2 day-" every 12 h on 2 days and 3 million IU/m 2 once a day on days 1, 3 and 5). The inpatient treatment was followed by a maintenance phase during which 0.3 million Cetus units/m 2 rlL-2 was given s.c. every 12 h on days 1 -5 and 3 million IUm -2 day -1 rlFN-~zb was administered on days 1, 3, and 5 on an outpatient basis. All but 3 patients completed the induction week and 6 weeks of outpatient therapy. No grade 3 or 4 toxicities occurred during the therapy. Therapy was discontinued for 3 patients because of rapid tumour progression. Of the 23 evaluable RCC patients, 3 exhibited a complete response and 4 displayed partial remission, 7 showed stable disease during 1-18 months (median = 5 months) of therapy, and progression was seen in 9. We conclude that vaccination with autologous tumour material combined with s.c. rIL-2 and rIFN-ctzb administration can induce regressions in patients with advanced RCC and that even in non-responding patients a more favourable course of the disease can be achieved.It has generally been doubted that active specific immunotherapy (ASI) can be successful in inducing regressions in human metastatic disease [5); indeed, many attempts using tumour-cell-derived preparations extensively tested on tumour-bearing patients during the 1970s and early 1980s were ineffectual [6] and have largely been abandoned.* To whom correspondence should be addressed However, several investigators assert that ASI can be an effective modality in the case of minimal residual turnout cell burdens [8,29], and accumulating clinical evidence suggests that appropriate immunization procedures can generate clinically meaningful ASI, especially against renal cell carcinoma [14,16,28,30]. The adjuvants with unspecific stimulatory activity utilized in these clinical studies included the bacillus CalmetteGu6rin [7, 30], Corynebacterium parvum [16,27,28], and the Newcastle disease virus [24].Animal studies have provided some evidence for the anti-tumour-activity of the agents in vivo [8,9,29]. It is desirable to improve the therapeutic effect of the cancer vaccines presenting presumably weakly immunogenic relevant antigens by selection of more suitable adjuvants. In a previous study we demonstrated that recombinant interleukin-2 (rIL-2) can serve as an effective adjuvant when administered with a renal cell carcinoma vaccine to post-nephrectomy patients with no remaining macroscopic evidence of the disease [24].In patients immunized with NDV plus IL-2, augmentation of the delayed-type hypersensitivity (DTH) response to ASI, including increased reaction to unmodified autologous tumour cells, was documente...

Lokalrezidive des Nierenzellkarzinoms in der Fossa renalis nach Tumornephrektomie

“…IE/Woche, IL2 2 X 3 Mill. Cetus Einheiten/m2/Woche, teilweise kombiniert mit einer aktiven spezifischen Immunisierung (ASI) mit autologen Nierentumorzellen, deren Aufarbeitung und Applikationsmodus in einer frühen Arbeit aus unserer Klinik beschrieben wurde (13 Auf der Suche nach Risikofaktoren für das Auftreten von Lokalrezidiven nach Tumornephrektomien in unserem Kollektiv zeigte sich eine gewisse Häufung von G3-(44,4%) und G2-(33,3%) Tumoren als auch von Primärtumoren mit den Stadien T 3a -(35%) und T 3b/c -(40%) Tumoren gegenüber 22,2 % Gl-, 25 % T 2 Und 0 T r Nierenzellkarzinomen. Auch das mediane Intervall bis zum Auftreten der Lokalrezidive war um so kürzer, je entdifferenzierter und lokal fortgeschrittener die Primärtumoren waren mit 35,5 (9-61) Monaten bei G2-, 12 ( greßfrei Überlebenden waren alle 3 Differenzierungsgrade und sowohl T 2 , T 3a als auch T 3b/c -Stadien in den Primärtumoren vor Auftreten der Lokalrezidive statistisch gleichmäßig verteilt vertreten.…”