Delving into the Latest Updates on BCG Live(Sanofi Pasteur SA) with Synapse

Overview

Basic Info

Drug Type

Oncolytic bacteria

Synonyms

BCG bladder cancer vaccine, Immucyst Intravesical, TheraCys

+ [2]

Target-

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

Bladder Cancer

Originator Organization

Sanofi Pasteur

Active Organization-

Inactive Organization

Sanofi Pasteur

ImmunityBio, Inc.

Drug Highest PhaseWithdrawn

First Approval Date

US (24 Feb 2000),

Bladder Cancer

RegulationOrphan Drug (JP)

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Primary upper tract carcinoma in situ (UTcis) is a rare disease whose diagnosis and natural history are poorly understood. Radical nephroureterectomy is the standard of care but in imperatives or selected cases, topical instillations of Bacillus Calmette-Guérin (BCG) may represent a good alternative. The aim of this study was to report the histologic response to BCG instillations for the treatment of biopsy-proven UTcis and to systematically assess the current evidence on topical BCG instillation for the treatment of UTcis. This is a retrospective analysis of patients with biopsy-proven UTcis treated with BCG instillation between 1995 and 2020 in an expert center. The initial diagnosis was performed by a standardized random biopsy scheme during ureterorenoscopy (URS) in patients with positive cytology but negative CT and bladder biopsies. BCG course consisted of 6 weekly instillation of 81 mg Immucyst (Sanofi Pasteur MSD AG, Baar, Switzerland). Administration techniques were single-J, double-J and nephrostomy tube. The primary outcome was the rate of complete histological response at the 3-month 2nd-look-URS. Kaplan-Meier analysis curves assessed recurrence- and progression-free survival. A total of 22 patients (23 renal units) were included. Twenty-one (91.3%) patients completed the planned 6-week instillation cycle. Only one major complication was recorded (renal tuberculosis). Twenty patients had a 3-month 2nd-look-URS, with a complete histological response achieved in 17/20 cases (85%). After a median time of follow-up of 40 months (30-62), 8/20 patients harbored disease recurrence, including 5 cases of disease progression (≥pT2). The main limitations are the retrospective and non-comparative design of the study. Our systematic review (CRD42022324876) identified 15 studies (289 renal units). UTcis suffers from the lack of a standardized definition, and considerable heterogeneity has been found in making the diagnosis and assessing the response to treatment. Our study is the first to propose a histological diagnosis of UTcis as well as a histological re-evaluation of the response to treatment. Topical instillations of BCG appear to be a promising alternative, avoiding radical treatment in the majority of cases.

01 Jun 2022·Journal for ImmunoTherapy of Cancer

BCG hydrogel promotes CTSS-mediated antigen processing and presentation, thereby suppressing metastasis and prolonging survival in melanoma

Article

Author: Chan, Alfred A ; Tang, Li ; Robatel, Steve ; Schenk, Mirjam ; Bäriswyl, Lukas ; Kremenovic, Mirela ; Feng, Bing ; Gruber, Thomas ; Lee, Delphine J

BackgroundThe use of intralesionalMycobacterium bovisBCG (intralesional live BCG) for the treatment of metastatic melanoma resulted in regression of directly injected, and occasionally of distal lesions. However, intralesional-BCG is less effective in patients with visceral metastases and did not significantly improve overall survival.MethodsWe generated a novel BCG lysate and developed it into a thermosensitive PLGA-PEG-PLGA hydrogel (BCG hydrogel), which was injected adjacent to the tumor to assess its antitumor effect in syngeneic tumor models (B16F10, MC38). The effect of BCG hydrogel treatment on contralateral tumors, lung metastases, and survival was assessed to evaluate systemic long-term efficacy. Gene expression profiles of tumor-infiltrating immune cells and of tumor-draining lymph nodes from BCG hydrogel-treated mice were analyzed by single-cell RNA sequencing (scRNA-seq) and CD8+T cell receptor (TCR) repertoire diversity was assessed by TCR-sequencing. To confirm the mechanistic findings, RNA-seq data of biopsies obtained from in-transit cutaneous metastases of patients with melanoma who had received intralesional-BCG therapy were analyzed.ResultsHere, we show that BCG lysate exhibits enhanced antitumor efficacy compared to live mycobacteria and promotes a proinflammatory tumor microenvironment and M1 macrophage (MΦ) polarization in vivo. The underlying mechanisms of BCG lysate-mediated tumor immunity are dependent on MΦ and dendritic cells (DCs). BCG hydrogel treatment induced systemic immunity in melanoma-bearing mice with suppression of lung metastases and improved survival. Furthermore, BCG hydrogel promoted cathepsin S (CTSS) activity in MΦ and DCs, resulting in enhanced antigen processing and presentation of tumor-associated antigens. Finally, BCG hydrogel treatment was associated with increased frequencies of melanoma-reactive CD8+T cells. In human patients with melanoma, intralesional-BCG treatment was associated with enhanced M1 MΦ, mature DC, antigen processing and presentation, as well as with increased CTSS expression which positively correlated with patient survival.ConclusionsThese findings provide mechanistic insights as well as rationale for the clinical translation of BCG hydrogel as cancer immunotherapy to overcome the current limitations of immunotherapies for the treatment of patients with melanoma.

01 Feb 2016·Progrès en UrologieQ4 · MEDICINE

Évaluation des effets indésirables des instillations endovésicales par BCG : implication potentielle de la souche utilisée ?

Q4 · MEDICINE

Article

Author: Gilsoul, J ; Pirson, M ; Legrand, F ; Sotorres Cabanillas, J L ; Roumeguère, T ; Holz, S

INTRODUCTIONIntravesical instillations of BCG represent an established treatment of high-risk non-muscle-invasive bladder cancer but also carry considerable toxicity. The aim of this work was to identify adverse effects, their impact on the treatment and the possible involvement of the BCG strain used.MATERIAL AND METHODSTo evaluate adverse events in terms of incidence, severity and moment of occurrence, we performed a retrospective analysis of all patients treated with BCG in our institution from 1998 to 2012.RESULTSOne hundred and forty-six patients were retained for analysis, 140 (95.9%) finished their first induction cycle. Thirty patients (20.6%) had to stop the treatment because of BCG-related adverse events, 80% of which happened during the first 3 BCG cycles (12 instillations). The strain used may have had a significant impact: 16 out of 42 patients (38.1%) treated with Connaught (Immucyst®) and 14 out of 104 patients (13.5%) treated with Tice (Oncotice®) had to stop treatment because of BCG related adverse events (P=0.0019) with an odds ratio of 2.83 (IC 95%: 1.52-5.23).CONCLUSIONBCG-related adverse events generally occur at the beginning of the treatment and therefore do not limit the use of BCG maintenance therapy. Good instillation practice and, in our series, the shift from Connaught to Tice strain enabled to significantly reduce BCG-related adverse events through time. The potential implication of the BCG strain used should be evaluated in prospective trials.

100 Deals associated with BCG Live(Sanofi Pasteur SA)

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bladder Cancer	Preclinical	US	Sanofi Pasteur	24 Feb 2000

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02207608 (CTgov)	Phase 2	Poisoning	30	BCG (Immucist®) (BCG Alone (Immucist®))	rafiolpnim(rchzfxkvcp) = slcwcmdyve txcdqfeexd (rlddppwipo, ddqptwenmv - duwfcauswb) View more	-	28 May 2015
				Hyaluronic Acid+BCG (Immucist®) (Hyaluronic Acid)	rafiolpnim(rchzfxkvcp) = bqupebubul txcdqfeexd (rlddppwipo, sasavyjpfb - xsglaocmnl) View more
1672 (AUA2012)	Phase 3	-	149	Onco-Tice	(lgertjhyfz) = tkcybujgzh smqeppratx (lcglnjryrx ) View more	-	01 Apr 2012
				ImmuCyst (BCG Connaught)	(lgertjhyfz) = hgzszsmntp smqeppratx (lcglnjryrx ) View more