Bacillus Calmette-Guérin Connaught Research Articles

The Comparison of Efficacy between the Connaught and Tice Strains of Bacillus Calmette-guérin in Patients with Non-muscle-invasive Bladder Cancer in Taiwan

Purpose: The purpose of the study is to compare the efficacy of Bacillus Calmette-Guérin (BCG) strains, Connaught (ImmuCyst®), and TICE (OncoTICE®) in patients with nonmuscle invasive bladder cancer (nMIBC). Materials and Methods: Patients with nMIBC who underwent transurethral resection between March 1997 and December 2017 were enrolled. TICE was used due to the Connaught strain shortage since 2012; hence, direct comparison of the two strains could not be performed. An intravesical instillation (IVI) regimen of mitomycin-C, doxorubicin, and cisplatin (MDP) was used as the reference for comparison. The MDP group was separated into two cohorts (MDP-1 and MDP-2) that matched the same time period of Connaught and TICE treatment. Patients who did not complete the IVI course before disease recurrence or progression or were not followed up for at least 24 months were excluded. Results: A total of 730 patients were included in the analysis. There were 67 (9.2%), 38 (5.2%), and 625 (85.6%) patients who received the Connaught, TICE, and MDP treatment, respectively. During a median follow-up duration of 59 months, the recurrence rates of the Connaught, MDP-1, TICE, and MDP-2 groups were 10.5%, 22.8%, 28.9%, and 23.0%, respectively. Both BCG groups had higher tumor grades and more instances of carcinoma in situthan their corresponding MDP cohorts. The Connaught and TICE strains had similar effects in preventing tumor recurrence (Connaught vs. MDP, P= 0.876; TICE vs. MDP, P= 0.556). In the multivariable Cox proportional hazard model that included all patients, the Connaught and TICE groups had a similar risk (hazard ratio = 0.784 and 0.850) of recurrence compared to the MDP protocol. Although progression events were more frequently noticed in the Connaught group, the small number of events limited the analysis. Conclusion: The BCG strains, Connaught and TICE, had similar efficacy in reducing bladder tumor recurrence in nMIBC patients. Both strains resulted in similar bladder recurrence-free survival rates to chemotherapeutic agents.

Recurrence Rate and Cost Consequence of the Shortage of Bacillus Calmette-Guérin Connaught Strain for Bladder Cancer Patients

BackgroundBetween 2013 and 2016, global production of bacillus Calmette-Guérin (BCG) was dramatically reduced due to the collapse of the factory producing BCG Connaught. ObjectiveTo evaluate the clinical and economic impact of BCG shortage on a cohort of non–muscle-invasive bladder cancer (NMIBC) patients treated during the period of restricted supply. Design, setting and participantsThis retrospective, before and after, cost-consequence study included patients with intermediate- and high-risk NMIBC. Those resected between November 2011 and September 2013 (control group) were compared with those resected between October 2013 and December 2016 (study group). Outcome measurements and statistical analysisThe primary endpoint was the rate of tumor recurrence from 30 d after transurethral resection to the end of follow-up at 24 mo; the secondary endpoints included the average cost of primary treatment, average cost of treatment of recurrence, and excess cost due to BCG shortage per patient. Results and limitationsA total of 402 patients were included: 191 in the control group and 211 in the study group. The rate of recurrence at 24 mo was significantly higher in the study group than in the control group (46.9% vs 16.2%; relative risk: 0.7, 95% confidence interval [0.60; 0.82]; p < 0.001). The increased cost due to the decrease in BCG production was estimated to be €783 per patient with a new diagnosis of NMIBC during the period of restricted supply. This is a retrospective analysis at the level of our unit. A more precise evaluation would require a study of a larger cohort of patients. ConclusionsThe shortage of BCG between October 2013 and December 2016 had a significant medical and economic impact; there was an increased rate of bladder cancer recurrence, and the total cost of care for intermediate- and high-risk NMIBC was higher. Patient summaryIn this report, we analyzed the medical and economic impact of bacillus Calmette-Guérin (BCG) shortage that occurred between 2013 and 2016. We found a significant increase of bladder cancer recurrence and progression, and an increase in the number of patients who had to be treated by cystectomy. BCG shortage also had a significant impact on the total cost. Since there are no alternatives to BCG for high-risk non–muscle-invasive bladder cancer patients, BCG production has to be maintained by any means.

Bacillus Calmette-Guérin induces rapid gene expression changes in human bladder cancer cell lines that may modulate its survival.

Bacillus Calmette-Guérin (BCG) immunotherapy is the standard therapy for non-muscle invasive bladder cancer. The aim of the present study was to identify genes that are induced in response to BCG immunotherapy, as these may be potential biomarkers for the response to clinical therapy. To model clinical therapy, human bladder cancer cell lines were incubated with BCG (live or lyophilized BCG Connaught) for 2 h. RNA was extracted and evaluated by Representational Differential Analysis (RDA) and oligo arrays. Gene expression was confirmed by reverse transcription polymerase chain reaction on fresh cell lines with differential abilities to internalize BCG. The effect of 2 major BCG soluble proteins, antigen 85B (Ag85B) and Mycobacterium protein tyrosine phosphatase A (MptpA) and BCG Tice® on gene expression was also determined. GAPDH and β-actin, which are normally used as control genes, were upregulated by BCG. Therefore, the ribosomal RNA gene ribosomal protein S27a was used to normalize gene expression. The genes likely to be induced by BCG internalization and soluble factors were: GSTT2, MGST2, CCL20, TNFα, CCNE1 and IL10RB. Those induced by BCG membrane interactions and/or soluble factors were: MGST1, CXCL6, IL12A, CSF2, IL1β and TOLLIP. MptpA decreased GSTT2 expression, and Ag85B increased TNFα expression. The two BCG strains significantly increased GSTT2, TNFα and TOLLIP levels in MGH cells. However, in J82 cells there was a BCG strain-dependent difference in TNFα expression. An important outcome of the present study was the determination that neither GAPDH nor β-actin were suitable control genes for the analysis of BCG-induced gene expression. BCG Connaught and Tice® induced similar expression levels of genes in bladder cancer cell lines. BCG soluble proteins modulated gene expression and therefore may affect therapeutic outcomes. The genes identified may be novel biomarkers of the response to BCG therapy.

Does switching the bacillus Calmette-Guérin strain affect clinical outcome in patients with recurrent non–muscle-invasive bladder cancer after initial bacillus Calmette-Guérin therapy?

PurposeIt is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor). Materials and methodsWe retrospectively reviewed the clinicopathological features of 97 patients treated with a second induction course of BCG therapy between 1986 and 2014. Among the patients initially treated with BCG Tokyo-172, the second course was either BCG Tokyo-172 in 56 (57.8%) or BCG Connaught in 15 (15.5%). Among those who were initially treated with BCG Connaught, the corresponding numbers were 13 (13.4%) or 13 (13.4%), respectively. Twenty-eight (28.9%) patients were given a different BCG strain at the 2 BCG therapies (switching group), and 69 (71.1%) patients were given the same BCG strain (non-switching group). ResultThe 5-year recurrence-free survival rate of the switching group was 64.7 ± 9.6%, which was not significantly different from that of the non-switching group (54.8 ± 6.9%, P = 0.427). Switching or not switching the BCG strain was not significantly associated with tumor recurrence after the second BCG therapy. The 5-year progression-free survival rate of the switching group was 95.4 ± 2.6%, which was also not significantly different from that of the non-switching group (96.0 ± 3.9%, P = 0.674). Patients treated with BCG Tokyo-172 to Tokyo-172 had significantly higher incidences of side effects during the second BCG therapy. ConclusionsThe results of this study indicate that in patients with a BCG-relapsing tumor after the initial BCG therapy, the same BCG strain as that administered at the initial BCG therapy could be utilized effectively for the second BCG therapy. Patients treated with BCG Tokyo-172 for an initial tumor had a higher incidence of side effects during the second BCG therapy using the same strain.

The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non–muscle-invasive bladder cancer

BackgroundPotential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. ObjectiveTo retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non–muscle-invasive bladder cancer patients. Design, setting, and participantsIndividual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. Outcome measurements and statistical analysisUsing Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. Results and limitationsInformation on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20–1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47–0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14–0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. ConclusionsWe found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. Patient summaryAs there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.

Bacillus Calmette-Guérin Strain Differences Have an Impact on Clinical Outcome in Bladder Cancer Immunotherapy

BackgroundWhether the commonly used bacillus Calmette-Guérin (BCG) strains Connaught and Tice confer different treatment responses in non–muscle-invasive bladder cancer (NMIBC) is unknown. ObjectivesTo compare clinical efficacy, immunogenicity, and genetics of BCG Connaught and Tice. Design, setting, and participantsA prospective randomized single-institution trial with treatment of 142 high-risk NMIBC patients with BCG Connaught or Tice. InterventionPatients were randomized to receive six instillations of BCG Connaught or Tice. For experimental studies, BCG strains were compared in C57Bl/6 mice. Bladders and lymphoid tissues were analyzed by cytometry and the latter cultivated to detect live BCG. BCG genomic DNA was sequenced and compared with reference genomes. Outcome measurements and statistical analysisRecurrence-free survival was the primary end point of the clinical study. The Kaplan-Meier estimator was used for estimating survival and time-to-event end points. Nonparametric tests served for the analysis of the in vivo results. Results and limitationsTreatment with BCG Connaught conferred significantly greater 5-yr recurrence-free survival compared with treatment with BCG Tice (p=0.0108). Comparable numbers of patients experienced BCG therapy-related side effects in each treatment group (p=0.09). In mice, BCG Connaught induced stronger T-helper cell 1–biased responses, greater priming of BCG-specific CD8+ T cells, and more robust T-cell recruitment to the bladder than BCG Tice. Genome sequencing of the BCG strains revealed candidate genes potentially involved in the differential clinical responses. ConclusionsBCG strain may have an impact on treatment outcome in NMIBC immunotherapy. Patient summaryWe compared the efficacy of two commonly used bacillus Calmette-Guérin (BCG) strains for the treatment of NMIBC and found that treatment with BCG Connaught prevented recurrences more efficiently than BCG Tice. Comparison of the immunogenicity of the two strains in mice indicated superior immunogenicity of BCG Connaught. We also identified genetic differences that may explain the differential efficacy of the Connaught and Tice BCG strains. Trial registrationNCT00003779.

Abstract 5386: Immunotherapy of bladder cancer using bacillus calmette guérin (BCG): Generation of cytotoxic T-cells is BCG strain dependent

Abstract Introduction: Forty years ago Zbar and colleagues demonstrated that bacillus calmette guérin (BCG) is capable of provoking an immune response against experimentally induced tumors. The conditions for successful tumor immunity were defined by a i) limited number of tumor cells in ii) close contact with a iii) sufficient number of bacteria and iv) the ability of the organism to mount a BCG specific immune response. These findings led to the development of what is currently the standard of care for the treatment of patients with non-muscle invasive bladder cancer. Whether the genetic drift between BCG strains that are routinely used in treatment protocols for bladder cancer affects the generation of successful tumor immunity is unknown. Here we compared two of the commonly used BCG strains (Connaught and Tice) in the treatment of bladder cancer in an animal model. Methods: Naïve or bladder cancer bearing (orthotopic implantation of syngeneic MB49 cells) Bl/6 mice received either a single s.c. injection or weekly intravesical instillation of 107 CFUs of BCG Tice or Connaught. Twelve days after the 4th intravesical treatment or after the single s.c. immunization, the bladders, spleens and draining lymph nodes (DLN) were removed, enzymatically digested and the resulting cell suspensions analyzed by flow cytometry, including assessment of BCG specific CD8+ T-cells. Lymph node extracts were cultivated for the enumeration of BCG CFUs. Tumor bearing animals were assessed for their overall survival. Results: In non-tumor bearing animals, BCG Connaught lead to a more robust influx of adaptive immune cells into the bladder and primed significantly more BCG specific cytotoxic CD8+ T-cells. Compared to BCG Connaught, BCG Tice was less capable to disseminate into the draining lymph nodes (DLN), and induced less Th1 polarized CD4+ T-cells in the bladder, DLN and spleens, as assed by intracellular T-bet staining. These findings were independent of BCG preparation (clinical grade versus laboratory grade) and were seen for identical treatment doses. Finally, mice, orthotopically challenged with MB49 bladder cancer cells, showed significantly better survival if treated with BCG Connaught as compared to BCG Tice. Conclusion: Here we show that different BCG strains significantly impact the immunological response of adaptive immunity. Along with a stronger Th1 immune response, favoring the generation of cytotoxic T-cells, BCG Connaught improves survival as compared to BCG Tice in vivo. These findings implicate potential consequences for clinical practice and corroborate testing of different BCG strains in prospective clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5386. doi:1538-7445.AM2012-5386

Abstract 2691: A randomized Phase III study comparing the efficacy of Bacillus Calmette Guérin strain Tice versus Connaught for immunotherapy of non-muscle invasive bladder cancer

Abstract Introduction: For almost forty years now, adjuvant immunotherapy with intravesical Bacillus Calmette Guérin (BCG) is standard of care in the treatment of non-muscle invasive bladder cancer (NMIBC). The question whether the choice of the different available BCG strains used for treatment influences treatment outcome is still under debate. We report on a randomized phase III study comparing the two most commonly used strains in Europe and the USA. Patients and Methods: This study was performed under approval of the Cantonal Ethical Committee of Bern, Switzerland, to evaluate recurrence free survival in patients treated with BCG as the primary end-point. Between 1998 and 2010 149 patients (n=149) were recruited. Patients underwent transurethral resection of all visible bladder tumors or random bladder biopsies in case of a solely positive bladder wash cytology. TaG3 and T1G3 tumors underwent a second resection to confirm non-muscle invasive disease. Two to 15 days after surgery, patients were either randomized to receive six weekly intravesical instillations with 2-8x108 CFU OncoTice ® (BCG Tice) or 6.6-19.2 x108 CFU ImmuCyst ® (BCG Connaught) dissolved in 50 ml of saline according to manufacturers recommendations. Patients were followed in 3-monthly intervals for 3yrs, then in 6-monthly intervals by cystoscopy and bladder wash cytology. Relapses were confirmed by histology after transurethral surgery. Cox regression analysis and Log rank tests served for statistical analysis. Results: Gender, age, tumor stage and grade were well balanced between the two treatment arms (p=0.38). Median follow up was 25 months (range: 0.3-136). Side effects did not differ between the two treatment arms (p=0.42). Age and gender did not have an impact on treatment response (p=0.71). Five year recurrence-free survival for all patients was 61%. Patients treated with Connaught had significantly less recurrences than patients treated with OncoTice (p&amp;lt;0.002). Five year recurrence-free survival was 75% and 46% for Connaught and Tice treated patients, respectively. Median recurrence-free survival was 28 months (range: 0.6-136) for Connaught and 22 months (range: 0.3-122) for Tice treated patients. Progression-free and overall survivals were not significantly different between the two treatment arms. Conclusions: The choice of the BCG strain impacts on treatment outcome and favors the use of BCG Connaught over Tice in the treatment of NMIBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2691. doi:1538-7445.AM2012-2691

Female Gender and Carcinoma In Situ in the Prostatic Urethra Are Prognostic Factors for Recurrence, Progression, and Disease-Specific Mortality in T1G3 Bladder Cancer Patients Treated With Bacillus Calmette-Guérin

BackgroundControversy exists over the most important prognostic factors in T1 high-grade non–muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG). ObjectiveEvaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up. Design, setting, and participantsA single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC. InterventionAll patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81mg) without maintenance therapy. MeasurementsThe variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions. Results and limitationsThe median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p=0.0003, HR: 2.53), progression (p=0.001, HR: 3.59), and death due to BCa (p=0.004, HR: 3.53). ConclusionsIn primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.

Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model.

Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette-Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recombinant BCG vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of TB. We have tested the efficacy of the two strains in the highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB. Animals immunized with the recombinant BCG vaccines and challenged by aerosol with a highly virulent strain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG vaccine counterparts. Statistically, these differences were highly significant. Paralleling these results, at necropsy, animals immunized with the recombinant BCG vaccines had fewer and smaller lesions in the lung, spleen, and liver and significantly less lung pathology than animals immunized with the parental BCG vaccines. The recombinant vaccines are the first vaccines against TB more potent than the current commercially available BCG vaccines, which were developed nearly a century ago.

In situ transitional cell carcinoma involvement of prostatic urethra: Bacillus calmette-guérin therapy without previous transurethral resection of the prostate

Bacillus Calmette-Guérin (BCG) has demonstrated both the efficacy in patients with carcinoma in situ (CIS) of the bladder and the penetration in the prostate (granulomas) after endovesical treatment. We treated patients with CIS of the prostatic urethra with bladder instillations of BCG without previous transurethral resection to assess the local therapeutic effect. Eighteen patients with CIS of the prostatic urethra (15 multifocal CIS and 15 associated to superficial bladder carcinoma) were treated with endovesical instillations of 81 mg of BCG Connaught weekly for 6 weeks. After a mean follow-up of 31 months, 14 of 18 patients had complete response, 3 had progression (2 in the prostate and 1 in the bladder); diffuse CIS of the bladder persisted in 1 patient. Three patients required cystectomy and 1 underwent palliative transurethral resection. Fifteen patients are alive with no evidence of disease, 2 patients died due to progression of the disease, and 1 is alive with tumor. The presence of CIS in the prostatic urethra can be managed with endovesical BCG as initial treatment with fairly good success. There is no need for transurethral resection, even though a loop biopsy may have to be obtained at the first control examination to make sure there is no stromal invasion.

BCG in perspective: advances in the treatment of superficial bladder cancer.

The management of superficial bladder cancer has advanced significantly in recent years. Controlled clinical trials suggest the benefits of cytotoxic chemotherapy apply primarily to well-differentiated tumours, are short-term and do not include a reduction in disease progression. In contrast, intravesical bacillus Calmette-Guérin (BCG) immunotherapy is effective in high-grade tumours, provides long-term protection from tumour recurrence and reduces disease progression. Controlled clinical trials have consistently demonstrated that BCG provides superior protection from tumour recurrence compared with thiotepa or doxorubicin. In comparisons with mitomycin C, only two of six studies found a significant advantage for BCG therapy; both studies evaluating high-risk patients showed a significant reduction in tumour recurrence with BCG compared with mitomycin C. Controlled trials have demonstrated that newer chemotherapies and more intensive regimens are not superior to standard thiotepa treatment. However, controlled comparisons of immunotherapy suggest that BCG is superior to both interferon and keyhole-limpet haemocyanin. Comparative studies showing BCG to be superior to chemotherapy and other immunotherapies have employed what we now know to be suboptimal BCG regimens. Using three additional weekly BCG (Connaught) treatments at 3 months, complete response in carcinoma in situ is increased from 73 to 87%. In patients who are disease free, maintenance BCG using three weekly treatments at 6-month intervals improves long-term disease-free status in stage Ta and T1 bladder cancer from 50 to 83%. Such maintenance therapy improves the excellent 86% survival obtained with a single 6-week course of BCG to 92% (p < 0.04).

The Effects of Intravesical Pretreatment with Pentosan Polysulfate on the Bacillus Calmette-Guérin Induced Immune Reaction of the Guinea Pig

Immunotherapy with intravesical instillation of bacillus Calmette-Guérin (BCG) is an effective treatment for superficial bladder carcinoma. In the present study the BCG-induced immunological reaction in the guinea pig (PPD skin test, bladder wall infiltrates and number of cells in the iliac lymph nodes) was investigated after intravesical pretreatment with pentosan polysulphate (PPS), which modulated BCG attachment to the bladder wall. Pentosan polysulfate is a molecule comparable to the naturally occurring glycosaminoglycans (GAGs) of the bladder mucosa. The data obtained after six weekly instillations of BCG-RIVM (5 × 106 — 5 × 107 cfu) with or without preinstillation with PPS (10mg. in 1ml. for 0.5 hour) suggested an elevation of the immunological reaction to intravesical BCG. A strong binding capacity of PPS to the mammalian bladder wall was observed. In addition, and in contrast to bacteria commonly causing cystitis, a significant binding of PPS to mycobacteria was found: 3.5, 3.6 and 3.1μg./ml. dry weight of BCG Connaught, RIVM and Pasteur, compared with 0.2, 0.3, 0.7 and 0.0μg./mg. dry weight of Escherichia coli, Streptococcus faecalis, Klebsiella pneumoniae and Proteus.The results suggest that PPS enhances the attachment of BCG to the bladder wall, resulting in an increased BCG-induced immunological reaction in the guinea pig. It may be speculated that pretreatment with PPS may increase the efficacy of BCG therapy in man, especially in those patients not exhibiting an immunological reaction.