Human toxicology of BCG applied in cancer immunotherapy

Schwarzenberg, L; Simmler, Marie‐Christine; Pico, J L

doi:10.1007/bf00205297

Cited by 33 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has to be stressed that these effects are observed at relatively high doses which may not be relevant to clinical treatment. However, fever and liver granulomas are also reported in patients treated with BCG [13,27].…”

Section: Discussionmentioning

confidence: 89%

Experimental screening of two BCG preparations produced according to different principles

Kreeftenberg

Jong

Ettekoven

et al. 1981

Cancer Immunol Immunother

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 89%

Experimental screening of two BCG preparations produced according to different principles

Kreeftenberg

Jong

Ettekoven

et al. 1981

Cancer Immunol Immunother

View full text Add to dashboard Cite

“…Disadvantages of BCG therapy are the reported side effects such as septicemia, hepatic dysfunction due to tuberculoma-like granulomas, death from hypersensitivity, painful local infections and the possibility of enhancing tumor growth or metastases (Schwarzenberg et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

The effect of Keyhole Limpet Hemocyanin (KLH) on the rat bladder

Klippel¹,

Paulini²,

Hutschenreiter³

1977

Cancer Immunol Immunother

View full text Add to dashboard Cite

Summary. Immunostimulation with agents such as BCG or K L H may represent an adjuvant therapy in treating patients with bladder cancer. To investigate the effects of direct instillation and injection of K L H into the bladder of sensitized and nonsensitized rats, K L H was injected Olsson et al. (1973) were able to show statistically significant immunologic reduction in the bladder cancer recurrence rate by immunizing patients with 5 mg K L H (keyhole limpet hemocyanin) intracutaneously. Attempts have also been made to enhance patients' immunreactivity by injecting B C G intralesionally after previous subcutaneous sensitation. In a toxicity study, we tried to obtain information about the histological reactions of K L H injected into the rat bladder, using the same experimental model as Bloomberg et al. (1975), who injected B C G into the dog bladder. Material and MethodsSixty postpuberal male and female syngenic Wistar rats weighing 168-245 g were divided into two treatment groups: Group I consisted of 30 rats which received no KLH stimulation before KLH injection into the bladder. Group II consisted of 30 rats which were sensitized with two injections of KLH to provoke lymphocyte reacReprint requests should be addressed to: K. F. Klippel tivity. Each rat of Group II received two injections of 0.1 mg KLH s.c. (Calbiochem. 374805, A grade) one week apart, stabilized prior to injection by phosphate buffered saline 0.005 M pH 8.5 in order to obtain the dissociated state (pH 8.6) with fractions of a molecular weight of about 1 million (S 18).Groups I and II were further subdivided into three identical treatment groups of 10 animals each:Sub-groups Ia, IIa: Submucosal injection of sterile normal saline by direct bladder exposure (0.3 ml).Sub-groups Ib, IIb: KLH-instillation 0.5 ml (= 12.5 mg) into the bladder via a polyethylene catheter O 1 ram, left in place for 10 min during anesthesia.Sub-groups Ic, IIc: Submucosal KLH-injection 0.2 ml (= 5 mg) by direct bladder exposure.Anesthesia was induced by ether and continued by Nembutal® 0.2 mg/kg. Three weeks after treatment, the animals were sacrificed and the bladders surgically removed. ResultsThere was no animal mortality. Intradermal injection of K L H was well-tolerated and showed a mild inflammatory reaction at the skin site in only seven rats. Histological studies on the bladders of the saline-injected animals (Groups Ia and IIa) showed mild vascular congestion and fibrosis consistent with the operative procedure. Nonsensitized rats (Ib) with K L H instillation showed no marked reaction, whereas bladders of the sensitized rats (IIb) showed a slight vascular reaction.The ten nonsensitized rats which received direct injections of K L H (Group Ib) showed mild vascular congestion histologically and activation of flbrocytes with loosely structured nuclei. The mononuclear cell infiltration was equally present in all animals of this group.The animals in Group IIc, pre-sensitized with K L H injections, showed a marked inflammatory reaction with leucocyte infiltration, acti...

show abstract

“…The routes and methods of administration include oral [5], IV [16,18], intralymphatic [25], intratumoral [28,29,30,32], ID [3], Heafgun technique [33], the tine plate method [28], scarification [3,7,8,9], and intrapleural [23,24]. There have been significant clinical problems and some fatalities [15,36,37,39,40]. The use of BCG in immunotherapy has not been without untoward side effects [38].…”

Section: Discussionmentioning

confidence: 99%

Active specific immunotherapy of residual micrometastasis

Hanna

Brandhorst

Peters

1979

Cancer Immunol Immunother

View full text Add to dashboard Cite

A vaccine of Bacillus Calmette-Gu~rin (BCG) admixed with tumor cells induced systemic immunity and had a therapeutic effect on subclinical, disseminated mierometastasis. Inbred strain-2 guinea-pigs given I V injections of 5 x 103 to 106 syngeneic LIO hepatocarcinoma cells were vaccinated after metastatic foei were established in the lung parenchyma. The purpose of this study was to establish the variables that can be manipulated to assure optimal immunotherapy while minimizing deleterious side effects of the BCG. In the present study we examined the variables of source, dose, and ratio of BCG to tumor cells. Four BCG sources (lyophilized Tiee and Connaught; fresh-frozen Phipps and Tice) were compared. No significant differences among these BCG preparations couM be detected with respect to adjuvant potential when they were admixed with attenuated tumor cells in a vaccine. The dose study clearly demonstrated that a BCG dose dependency exists with relation to induction of effective cell-mediated immunity or survival from disseminated mierometastatic disease. Furthermore, evaluations of dose versus ratio of BCG to tumor cells also supported a BCG dose dependency, with the lowest effective BCG dose being directly influenced by tumor burden of the host. Cutaneous reactivity and hypersensitivity of the primary and secondary immunization sites of tumor-bearing animals treated with effective and ineffective vaccines supported the direct association of reaction to BCG and specific tumor immunity. However, when an in vitro leukocyte migration inhibition assay was used, the degree of reactivity to BCG could not be exploited as a quantitative, diagnostic monitor of effective systemic tumor immunity.

show abstract

Human toxicology of BCG applied in cancer immunotherapy

Cited by 33 publications

References 19 publications

Experimental screening of two BCG preparations produced according to different principles

Experimental screening of two BCG preparations produced according to different principles

The effect of Keyhole Limpet Hemocyanin (KLH) on the rat bladder

Active specific immunotherapy of residual micrometastasis

Contact Info

Product

Resources

About