Experimental Screening of BCG Preparations Produced for Cancer Immunotherapy: Safety and Immunostimulating and Antitumor Activity of Four Consecutively Produced Batches

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 1984 Jan 1

PMID 6563941

Citations 10

Authors

W H De Jong

P A Steerenberg

J G Kreeftenberg

R H Tiesjema

W Kruizinga

L M VAN NOORLE JANSEN

E J Ruitenberg

Affiliations

Soon will be listed here.

Abstract

Four consecutively produced batches of Bacillus Calmette-Guérin (BCG) especially intended to be used for cancer immunotherapy were investigated for consistency of the vaccine. Each batch was investigated directly after production of the vaccine, so that the four batches were not tested simultaneously. The activity of the four batches was investigated in general safety assays, immunostimulation assays, and two different tumor models. General safety assays showed dose-dependent growth retardation and increased serum glutamic pyruvic transaminase activity in mice, and a long-lasting temperature rise in rabbits after IV administration of the BCG preparations. In a skin reactivity assay, reactions were found acceptable for all preparations when compared with a reference batch. The results of the immunostimulation and antitumor studies can be summarized as follows. All four batches induced a specific delayed-type hypersensitivity reaction to PPD, indicating the induction of cell-mediated immunity. A stimulating effect on lymphoreticular organs was concluded from increased spleen weight and enhanced cell proliferation in draining lymph nodes. Enhanced macrophage function (phagocytosis and killing of bacteria) was demonstrated by an increased resistance to Listeria monocytogenes. YAC lymphoma target cells were killed nonspecifically by BCG-activated peritoneal exudate cells (PEC), indicating the induction of natural killing activity by BCG. Intralesional injection of BCG induced tumor regression in the guinea pig line 10 hepatocellular carcinoma, followed by immunity to the line 10 tumor. In the murine 5D04 squamous cell carcinoma, BCG had no effect on the primary tumor. However, IV-injected BCG resulted in a decreased number of lung metastases. In general, the four consecutively produced batches showed similar safety and activity in the immunostimulation assays and antitumor activity. Since only minor differences between the batches were found, which can also be attributed to the variation in experimental conditions common to biological assays, it is concluded that the vaccine batches produced show an acceptable consistency.

Citing Articles

Experimental screening of BCG preparations produced for cancer immunotherapy: safety and immunostimulating and antitumor activity of four consecutively produced batches.

De Jong W, Steerenberg P, Kreeftenberg J, Tiesjema R, Kruizinga W, VAN NOORLE JANSEN L Cancer Immunol Immunother. 1984; 17(1):18-27.

PMID: 6563941 PMC: 11039122. DOI: 10.1007/BF00205492.

The effects of intravesical and intradermal application of a new B.C.G. on the dog bladder.

vd Meijden A, Steerenberg P, De Jong W, Bogman M, Feitz W, Hendriks B Urol Res. 1986; 14(4):207-10.

PMID: 3787886 DOI: 10.1007/BF00441115.

Equine sarcoid: BCG immunotherapy compared to cryosurgery in a prospective randomised clinical trial.

Klein W, Bras G, Misdorp W, Steerenberg P, De Jong W, Tiesjema R Cancer Immunol Immunother. 1986; 21(2):133-40.

PMID: 3633215 PMC: 11038812. DOI: 10.1007/BF00199861.

Immunological aspects of intravesical administration of Bacillus Calmette-Guérin (BCG) in the guinea pig.

van der Meijden A, De Jong W, de Boer E, Steerenberg P, Debruyne F, Ruitenberg E Urol Res. 1989; 17(1):47-55.

PMID: 2922891 DOI: 10.1007/BF00261051.

Major-histocompatibility-complex-class-II-positive cells and interleukin-2-dependent proliferation of immune T cells are required to reject carcinoma cells in the guinea pig.

Steerenberg P, De Jong W, Geerse E, Beuvink A, Scheper R, Den Otter W Cancer Immunol Immunother. 1990; 31(5):297-304.

PMID: 2376047 PMC: 11038608. DOI: 10.1007/BF01740938.

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