Liposome formulations for the treatment of cancer

Abstract

The present invention relates to a therapeutic agent based on cell wall fragments of a virulent strain of Mycobacterium tuberculosis-complex for use in the treatment of cancer.

Description

[0001] LIPOSOME FORMULATIONS FOR THE TREATMENT OF CANCER FIELD OF THE INVENTION The present invention relates to the use of a therapeutic agent based on cell wall fragmentsof a virulent strain of Mycobacterium tuberculosis-complex for the preparation of a drug forthe treatment of cancer in human subjects. BACKGROUND OF THE INVENTION According to the Global cancer observatory (GLOBOCAN) report from 2022, cancer remains a major health challenge with 19,976,499 new cases and 9,743,832 deaths worldwide. For instance, bladder cancer has the tenth highest incidence of cancers worldwide and is associated with 573,278 new cases and 212,536 deaths annually. Bladder cancer incidence is steadily augmenting worldwide, especially in developed nations, and it has the highest lifetime treatment cost of all cancers. Approximately 75% of bladder cancer cases are classified as non- muscle invasive bladder cancer (NMIBC), a cancer associated with high rates of recurrence (30–80%) and a risk of progression to invasive and metastatic cancer (see, e.g., GLOBOCANreport from 2021 and Babjuk M. et al., “EAU Guidelines on Non–Muscle-invasive UrothelialCarcinoma of the Bladder: Update 2013”, Eur Urol . 2013 Oct;64(4):639–53). Standard treatment for high-risk NMIBC includes transurethral resection of the bladder tumor (TURBT), followed by intravesical Bacillus Calmette–Guérin (BCG) therapy (Morales, A., Eidinger, D. & Bruce, A. W. Intracavitary Bacillus Calmette Guerin in the treatment of superficial bladder tumors. Journal of Urology 116, 180–182 (1976)). BCG is an attenuated strain of Mycobacterium bovis, which has proven to be an efficient therapeutic vaccine and is used asthe gold standard treatment of bladder cancer (Guallar-Garrido et al., 2020, ImmunoTargetsand Therapy 9, 1–11). However, 30%-50% of patients fail to respond to BCG, and 10%-15% progress to muscle-invasive bladder cancer (MIBC) often requiring aggressive salvage therapies, such as cystectomy (Sylvester, R. J. et al. Long-Term Efficacy Results of EORTC Genito-Urinary Group Randomized Phase 3 Study 30911 Comparing Intravesical Instillations of Epirubicin, Bacillus Calmette-Guérin, and Bacillus Calmette-Guérin plus Isoniazid in Patients with Intermediate- and High-Risk Stage Ta T1 Urothelial Carcinoma of the Bladder. Eur Urol 57, 766–773 (2010). Moreover, BCG has shown efficacy when used as a therapeutic agent for the treatment of further cancer types such as melanoma and breast cancer (Gutterman et al.,1976, Cancer Immunol Immunother 1, 99–107; Kremenovic et al., 2020, J Intern Med, 288,625–640). Although BCG has been used for NMIBC since the 1990s, its mechanism of action remains unclear (Redelman-Sidi, G., Glickman, M. S. & Bochner, B. H. The mechanism of action of BCG therapy for bladder cancer-A current perspective. Nat Rev Urol 11, 153–162 (2014)). Failure of BCG treatment often entails aggressive therapies such as cystectomy, which can negatively impact survival. Thus, there is an urgent need to improve the treatment of bladder cancer, in particular to improve the response to BCG in bladder cancer patients. SUMMARY OF THE INVENTION The present inventors have found that an agent based on cell wall fragments of a virulentstrain of Mycobacterium tuberculosis-complex (MTB-C) is highly effective in the treatment ofcancer, in particular when used as prime vaccination for standard BCG treatment of cancer, such as bladder cancer. Many parameters can contribute to the efficiency of vaccines in general, such as the type of the vaccine, the adjuvants, the dose, the route of administration, the number of injections, and the delay between applications. In the particular case of heterologous prime-boost strategies, the combination and the order of vaccines further need to be determined. To date, as the exact molecular mechanisms promoting vaccine efficiency in general are not well understood, the development of novel efficient vaccination strategies is very challenging. Therefore, providing novel and efficient cancer vaccination therapies remains very challenging, due to an overall poor understanding of the molecular mechanisms involved in the generation of strong immune responses to the vaccines. Pre-administration of the agent (which is in the form of a liposome formulation, see below) according to the present invention was surprisingly found to enhance the immune response to BCG treatment and to increase the efficacy of BCG in cancer treatment of human patients. More precisely, the agent showed strong immunogenicity by itself and its use as prime for BCG treatment could be associated with a higher recurrence-free survival rate (RFS), a higher progression-free survival rate (PFS), a higher event-free survival rate (EFS), and a higher cancer-specific free survival rate compared to a placebo control group. The elongation of these parameters provides a broader time window in which harsh therapies can be reduced. The present invention provides the following items: [1] A liposome formulation comprising: (a) fragments from a Mycobacterium tuberculosis-complex (MTB-C) strain,(b) a liposome forming agent, and (c) 1 to 20 % (w / v) sucrose, wherein the z-average size of the particles is 150 nm or less, as determined by dynamic light scattering and the polydispersity index of the particles is 0.400 or less, for use in a method of treating cancer in a human subject. [2] The liposome formulation for use in a method of treatment according to item [1],wherein the Mycobacterium tuberculosis-complex (MTB-C) strain is a virulent Mycobacteriumtuberculosis-complex (MTB-C) strain, preferably the MTB-C strain NCTC 13536, deposited in 2010 at the NCTC in London. [3] The liposome formulation for use in a method of treatment according to items [1] or [2], additionally comprising (a) a tensioactive agent, and / or (b) one or more non-ionic surfactants. [4] The liposome formulation for use in a method of treatment according to any one of items [1]–[3], wherein the liposome forming agent is a hydrogenated, partially hydrogenated, or non-hydrogenated phospholipid, preferably wherein the liposome forming agent is soy lecithin. [5] The liposome formulation for use in a method of treatment according to any one of items [1]–[4], wherein the liposome formulation comprises at least two of the following polypeptides: (a) a polypeptide having a molecular weight of about 38 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis 38 kDaprotein (Rv 0934), (b) a polypeptide having a molecular weight of about 30-34 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis Ag85complex protein (Rv 1866c – Rv 3804c), (c) a polypeptide having a molecular weight of about 16 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis HSP 16.3protein (Rv2031c), (d) a polypeptide having a molecular weight of about 10 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis CFP10protein (Rv3874), and (e) a polypeptide having a molecular weight of about 6 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis ESAT-6protein (Rv3875). [6] A pharmaceutical composition comprising the liposome formulation as defined in any one of items [1]–[5] and a pharmaceutically acceptable carrier or diluent, and / or a pharmaceutically acceptable adjuvant, for use in a method of treating cancer in a human subject. [7] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–[6], wherein the cancer is a BCG-responsive cancer, preferably selected from: (i) bladder cancer, wherein preferably the cancer has been resected before said treatment, (ii) melanoma, and (iii) breast cancer. [8] The liposome formulation or pharmaceutical composition for use according to [7], wherein the cancer is bladder cancer. [9] The liposome formulation or pharmaceutical composition for use according to item [7(i)] or [8], wherein the bladder cancer is NMIBC, preferably high-risk NMIBC, wherein the pathological stage is preferably T1 or Ta, optionally associated to CIS.

[0010] The liposome formulation or pharmaceutical composition for use according to items [7(i)], [8] or [9], wherein the treatment results in a time to recurrence of at least 5 months, preferably at least 10 months, more preferably at least 15 months, even more preferably at least 20 months, wherein optionally, the time to recurrence is defined as the average time to recurrence observed for a clinical study group.

[0011] The liposome formulation or pharmaceutical composition for use according to any one of items [7(i)], [8], [9] or

[0010] , wherein the treatment results in an extended time to recurrence, wherein optionally, the time to recurrence is defined as the average time to recurrence observed for a clinical study group, wherein optionally, the time to recurrence is extended compared to an untreated control group, wherein optionally, (i) the time to recurrence is extended by a factor of at least two, or the time to recurrence is extended by a factor of at least three, preferably the time to recurrence is extended by a factor of at least four, or (ii) the time to recurrence is extended by at least any one of one to twenty months, optionally by nine months or by fifteen months.

[0012] The liposome formulation or pharmaceutical composition for use according to any one of items [7(i)]-

[0011] , wherein the treatment results in less than 25%, such as less than 20%, or less than 15%, preferably in less than 10%, such as less than 5%, or less than 2%, or 0% of progression to muscle-invasive disease (T2 or greater).

[0013] The liposome formulation or pharmaceutical composition for use according to any one of items [7(i)]-

[0012] , wherein the treatment results in a progression-free survival (PFS) of more than 73%, such as more than 75%, or more than 78%, such as more than 80%, or more than 85%, or more than 90%, or more than 95%, preferably of 100%.

[0014] The liposome formulation or pharmaceutical composition for use according to any one of items [7(i)]-

[0013] , wherein the treatment results in a cancer-specific free survival (CSS) rate of more than 84%, such as more than 85%, or more than 90%, such as more than 95%, or more than 97%, preferably of 100%.

[0015] The liposome formulation or pharmaceutical composition for use according to any one of items [7(i)]-

[0014] , wherein the treatment results in an event-free survival (EFS) rate of more than 50%, such as more than 60%, or more than 70%, such as more than 73%, such as more than 75%, or more than 80%, or more than 85%, preferably of 89.5%.

[0016] The liposome formulation or pharmaceutical composition for use according to any one of items [7(i)]-

[0015] , wherein the treatment results in a recurrence-free survival (RFS) rate of more than 73%, such as more than 75%, or more than 80%, or more than 84%, such as more than 85%, preferably of 89.5%, optionally wherein the treatment results in a RFS rate, calculated including all recurrences (both low- and high-grade) and any progression events occurring as the first event, of more than 56%, such as more than 60%, or more than 70%, or more than 75%, preferably more than 78%, such as 78.9%.

[0017] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–

[0016] , wherein the liposome formulation or pharmaceutical composition as defined in any one of items [1]-[6] is administered to the patient twice and wherein preferably, the second dose is administered 5-30 days after the first dose, such as 7-28 days after the first dose, preferably 7–10 days after the first dose, preferably 10 days after the first dose.

[0018] The liposome formulation or pharmaceutical composition for use according to of any one of items [1]–

[0017] , wherein the administration of said formulation or composition is parenteral, preferably subcutaneous.

[0019] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–

[0018] , wherein the treatment is therapeutic cancer vaccination, preferably prime- boost vaccination, more preferably heterologous prime-boost vaccination.

[0020] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–

[0019] , wherein the therapeutic cancer vaccination is a heterologous prime-boost vaccination, wherein the prime-boost vaccination comprises treatment with the liposome formulation as defined in item [1] and with BCG, and wherein preferably, the prime vaccine is the liposome formulation or pharmaceutical composition as defined in any one of items [1]- [6], and the boost vaccine is BCG treatment, preferably intravesical BCG treatment.

[0021] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–

[0020] , wherein the BCG treatment comprises i) an induction course, wherein BCG is administered six times in weekly intervals and, optionally ii) a maintenance course, wherein BCG is administered in three courses at three, six, and twelve months after the induction course as described in i) wherein optionally, the administration of BCG is intravesical and / or wherein optionally, each dose of BCG comprises 2–8 x 108colony forming units, optionally diluted in 50 mL sterile solution, wherein optionally, the liposome formulation or pharmaceutical composition as defined in any one of items [1]-[6] is applied before treatment with BCG, wherein optionally, the last dose of the liposome formulation or pharmaceutical composition as defined in any one of items [1]-[6] is administered 3 to 30 days before the day of the first treatment with BCG, preferably 6 to 15 days before the day of the first treatment with BCG, most preferably six days before the day of the first treatment with BCG.

[0022] The liposome formulation or pharmaceutical composition for use in a method of treatment according to any one of items [1]–

[0021] , wherein the liposome formulation or pharmaceutical composition is administered at a dose of 5–200 μg of FCMtb per dose, preferably at a dose of 25 µg per dose.

[0023] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–

[0022] , wherein the treatment comprises: i) Subcutaneous administration of 5–200 μg of FCMtb, preferably 25 µg of FCMtbto a patient diagnosed with a BCG-responsive cancer, preferably bladder cancer, more preferably NMIBC, even more preferably high-risk NMIBC, preferably after TURBT; ii) Subcutaneous administration of 5–200 μg of FCMtb, preferably 25 µg of FCMtbto the patient, wherein the administration takes place from 5-30 days after the first dose, such as from 7 to 28 days after the first dose, preferably from 7 to 10 days after the administration of i), preferably 10 days after the administration described in i); iii) Intravesical administration of a BCG induction course, wherein BCG is administered six times in weekly intervals, preferably wherein each dose of BCG comprises 2– 8 x 108colony forming units, wherein the first BCG dose is administered 3 to 30 days after the administration of ii), preferably 6 to 15 days after the administration of ii), even more preferably six days after the administration described in ii); and iv) Intravesical administration of a BCG maintenance course, wherein BCG is administered in three courses at three, six, and twelve months after the induction course described in iii), preferably wherein each dose of BCG comprises 2–8 x 108colony forming units.

[0024] The liposome formulation or pharmaceutical composition for use according to any one of items [1]–

[0023] , wherein the treatment comprises: i) Subcutaneous administration of 25 µg of FCMtb to a patient diagnosed withhigh-risk NMIBC after TURBT; ii) Subcutaneous administration of 25 µg of FCMtb to the patient, wherein theadministration takes place 10 days after the administration described in i); iii) Intravesical administration of a BCG induction course, wherein BCG is administered six times in weekly intervals, preferably wherein each dose of BCG comprises 2– 8 x 108colony forming units, wherein the first BCG dose is administered six days after the administration described in ii); and iv) Intravesical administration of a BCG maintenance course, wherein BCG is administered in three courses at three, six, and twelve months after the induction course described in iii), preferably wherein each dose of BCG comprises 2–8 x 108colony forming units. DEFINITIONS In the context of the present invention, "FCMtb" refers to cell wall fragments of aMycobacterium tuberculosis-complex (MTB-C) strain, i.e., to Mycobacterium tuberculosis cellwall fragments, preferably to cell wall fragments of MTB-C strain NCTC (“National Collection of Type Cultures”) 13536, as described herein and in the examples, e.g., Examples 2 and 3 and Figures 1 and 2. It constitutes the drug substance (DS) of the liposome formulation (drug product, DP) or pharmaceutical composition of the present invention. Strain NCTC 13536 was deposited at the National Collection of Type Cultures on December 3, 2010, by Archivel Farma S.L. “Liposome formulation” and “drug product”, herein used interchangeably, refer to the same item. The liposome formulation or drug product contains the drug substance or FCMtb. “Cancer vaccination” is a type of immunotherapy in which a vaccine (immunomodulator) is applied and modulates an immune response to stimulate the immune system to destroy or reduce a tumour. More specifically, “therapeutic cancer vaccination” or “therapeutic cancer vaccines” are used to treat a cancer or to prevent its development. “Prime-boost vaccination” is a vaccination strategy in which a vaccine product is applied more than once. The sequential administration of the same vaccination product is referred to as “homologous prime-boost” vaccination whereas the sequential administration of vaccines consisting of different delivery systems or even different vaccination products are referred to as “heterologous prime-boost” vaccination. The vaccination product applied first is referred to as “prime” or “prime vaccination” or “prime vaccine” whilst the subsequent vaccination product is referred to as “boost” or “boost vaccination” or “boost vaccine”. Both prime and boost vaccine may be applied each once or multiple times. “RUTI” or “RUTI®” refers to a particularly preferred embodiment of the liposome formulation (drug product) which comprises the drug substance (FCMtb), a liposome forming agent, and sucrose, which is optionally lyophilised for storage. RUTI® preferably comprises detoxified,pasteurized and liposomal cellular wall fragments of Mycobacterium tuberculosis (Mtb),preferably strain NCTC 13536 (see, e.g., Cardona P-J., “RUTI: A new chance to shorten the treatment of latent tuberculosis infection”, Tuberculosis, 2006 May;86(3–4):273–89). Hence,RUTI® comprises cellular wall fragments of Mycobacterium tuberculosis (Mtb), preferablystrain NCTC 13536, and optionally comprises one or more pharmaceutically acceptable carriers and / or excipients such as sucrose, soy lecithin, sodium cholate, sodium chloride, ethanol and / or water. The manufacture of RUTI® is described in the examples, e.g., Examples 2 and 3. Safety and tolerability profiles of the RUTI®vaccine in Clinical Trials was acceptable with the most frequent adverse events related to the site of injection. No relevant systemicchanges were observed in Phase I nor Phase II clinical trials (Vilaplana C. et al. “Double-blind,randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculousvaccine RUTI®”, Vaccine, 2010 Jan;28(4):1106–16 and Nell AS. et al., “Safety, tolerability, andimmunogenicity of the novel antituberculous vaccine RUTI: Randomized, placebo-controlled Phase II Clinical Trial in patients with latent tuberculosis infection”, Borrow R, editor. PLoS One, 2014 Feb 26;9(2):e89612). In a preferred embodiment, “RUTI®” is presented in vials and comprises the following components per vial:

[0002] Table 0. Preferred components of RUTI® per vialComponent Amount per vial FunctionDrug substance FCMtb 33.3 µg ImmunogenExcipients Sucrose 20,000.0 µgCharge substance (freeze-drying) and cryoprotector Soy lecithin1 422.9 µg Liposome forming agentSodium cholate 46.0 µg TensoactiveSodium chloride2 10.4 µg Isotonic agentEthanol3 q.s. SolventWater for injection q.s Solvent1Containing Phosphatidylcholine (NLT 94.0%) 2 Added as NaCl 0.9% solution 3It disappears in the course of processing “RUTI®” is a registered trademark from Archivel Pharma S.L. If lyophilized, RUTI® can be reconstituted for administration, e.g., in 0.4 mL of water for injection containing 83.3 μg / mL of FCMtb. “BCG” or “Bacillus Calmette-Guérin” refers to a therapeutic agent, for which ways of manufacture and formulation are well known to the person skilled in the art as they have been defined, e.g., by the WHO (World Health Organisation, Annex 2, “Requirements for dried BCGvaccine” in Requirements for Biological Substances No. 11, Revised 1985). The agent is basedon an attenuated strain of Mycobacterium bovis. Besides its use in the prevention oftuberculosis, BCG is an efficient vaccine for the treatment of cancer, such as bladder cancer. Intravesical BCG instillation is the gold-standard adjuvant immunotherapy for patients with high-risk non-muscle-invasive bladder cancer, and reference hospitals administer it to the suitable patients. BCG can be commercially obtained as different approved drug formulations(see, e.g., Guallar-Garrido et al., 2020, ImmunoTargets and Therapy 9, 1–11). Althoughsmaller studies without maintenance demonstrated some differences between strains, a network meta-analysis identified ten different BCG strains used for intravesical treatment in the published literature but was not able to confirm superiority of any BCG strain over another. Hence, no particular commercial strain or preparation has shown clinical superiority. The standard administration schedule is 1 weekly instillation for six weeks in induction course and 3 instillations at 3, 6 and 12 months as maintenance course (see, e.g., “EAU Guidelines onnon-muscle-invasive bladder cancer (TaT1 and CIS)”, P. Gontero et al., European Associationof Urology, 2023; Kapoor R. et al., “Bacillus Calmette-Guérin in the management of superficialbladder cancer”, Indian J Urol. 2008 Jan;24(1):72-6). No particular commercial strain or preparation has shown clinical superiority. BCG is administered one vial per 50 mL concentration under gravity with usual dwell time of two hours. For instance, one dose of BCG may comprise 81 mg lyophilized BCG, or 50 mg lyophilized BCG, which may be diluted with sterile preservative free saline up to a volume of 50 mL. One dose of BCG may also comprise less than 50 mg BCG, such as 27 mg BCG. Hence, in the context of the present invention, “BCG” or “BCG treatment” or “BCG therapy” encompasses any BCG product which is commercialized for the administration to patients, in particular for the administration to cancer patients such as bladder cancer patients or other patients suitable to be treated with BCG. "Particle size" refers to the diameter of the particles, unless otherwise specified. Where the particle size cannot be determined exactly, the approximate particle size is meant. "z-average" denotes the average particle size, determinable as described in the materials and methods section in this description. Preferably, the z-average particle size is (and in general for the size values throughout this specification) measured by dynamic light scattering (DLS), as described in detail in the materials and methods section in this description.The “polydispersity index” (pdi or PI) is a measure of the heterogeneity of a sample based onsize, determinable as described in the materials and methods section in this description. “Immunotherapy” refers to a set of treatment strategies that involve the modulation of the immune response. Active agents of immunotherapy are termed “immunomodulators” and they may be of natural, synthetic, or recombinant origin. Immunotherapy in the context of cancer treatment aims to stimulate the immune system to destroy tumours and / or prevent tumour development. “Tumour resection” refers to a surgery process for removing a tumour. In bladder cancer, it refers to a surgery to remove abnormal tissue (tumour) from the bladder through the urethra, termed transurethral resection of bladder tumour (TURBT). The standard initial treatment of non-muscle-invasive bladder cancer (NMIBC) is a transurethral resection of bladder tumor of all visible bladder lesions. This establishes the diagnosis and allows pathologic assessment of the resected tumor specimen for tumor grade, depth of bladder invasion, andpresence / absence of carcinoma in situ (Vögeli T-A., "The management of superficialtransitional cell carcinoma of the bladder: a critical assessment of contemporary concepts and future perspectives", BJU Int.2005; 96:1171–1176). T1 tumors are mostly high grade with a higher potential for progression and death. When treated with TURBT alone, T1 tumors havea high risk of progression to muscle invasion (see, e.g., Heney NM. et al., "Superficial bladdercancer: progression and recurrence", The Journal of Urology 1983; 130:1083–1086; PauwelsRP. et al., "Grading in superficial bladder cancer", (1). Morphological criteria. Br J Urol 1988;61:129–134; Abel PD, Hall RR, Williams G., "Should pT1 transitional cell cancers of the bladder still be classified as superficial?", Br J Urol 1988; 62:235–239). High-risk T1 tumors progress in more than 50% of cases; deaths from disease occur in 25% of patients in the first 5 years and in 10% of patients between 5 to 15 years (Herr HW., "Tumour progression and survival in patients with T1G3 bladder tumours: 15-year outcome", Br J Urol 1997; 80:762–765). “Non-muscle-invasive bladder cancer”, abbreviated as NMIBC, refers to a tumour which is restricted to the mucosa or lamina propria of the bladder. NMIBC represents a heterogeneous group of tumors with varying oncological outcomes according to two important features: recurrence and progression. The majority of bladder cancer (75%-85%) are initially diagnosed as non-muscle invasive bladder cancer (NMIBC), which has high recurrence rates (30%-80%)and a significant risk of progression to invasive disease (Gontero, P. et al. European Associationof Urology Guidelines on Non–muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)— A Summary of the 2024 Guidelines Update. Eur Urol (2024) doi:10.1016 / j.eururo.2024.07.027). NMIBC are stratified according to the risk of disease recurrence and progression into three groups: low-risk, intermediate-risk and high-risk tumors(Babjuk M. et al., "EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of theBladder: Update 2016", Eur. Urol.2016; :1–15). Tumor recurrence is quite common, occurring in as many as 60% to 90% of patients treated with surgery alone. “High-risk NMIBC” refers to a cancer which has a high propensity to grow and to recur after treatment. “Low-risk NMIBC” refers to a cancer which has a lower propensity to grow and to recur after treatment, and the type of NMIBC with the most favourable oncologic outcome. The progression and death rates associated with high-risk NMIBC are higher as compared to low-risk NMIBC. "Muscle-invasive bladder cancer”, abbreviated as MIBC, refers to a type of tumour in which the tumor has grown into the muscular layer of the bladder. … “Ta pathological stage”, “T1 pathological stage”, and “CIS” refer to different stages of NMIBC. NMIBC means the cancer cells are only in the inner lining of the bladder. There are 3 T stages of non-muscle invasive bladder cancer: Tis or CIS (also called carcinoma in situ), Ta and T1. Inthe Ta stage, the tumour is limited to the innermost layer of the bladder lining (papillarytumour without invading the bladder wall); in the T1 stage, the cancer has started to growinto the connective tissue beneath the bladder lining invading subepithelial connective tissue(tumour invades the connective tissue under the surface lining); in the CIS stage, the cancer isa flat, high-risk, non-papillary carcinoma which is confined to the urothelium. The CIS stage isalso referred to as Tis or carcinoma in situ. Generally, high-risk T1 and Ta tumours may or maynot be associated to CIS tumours. “Treatment courses” herein refers to different phases of treatments such as administration of a drug. The terms “induction course” and “maintenance course” herein refer to two different phases in which the patients receive BCG. The induction course constitutes the initial phase, which typically consists of six weekly administrations of BCG. The maintenance course is a subsequent maintenance therapy, typically consisting of three courses of weekly BCG for three weeks at 3, 6, and 12 months after induction. “Intravesical treatment” refers to a route of administration in which the active agent is applied into the bladder via a urethral catheter. “BCG-responsive cancer” or “BCG-responsive tumour” refers to any cancer or tumour which may respond to the treatment with BCG, i.e., which is susceptible to be treated with BCG, as defined herein. For instance, bladder cancer, e.g., high-risk NMIBC is a BCG-responsive cancer(Guallar-Garrido et al., 2020, ImmunoTargets and Therapy 9, 1–11). Breast cancer andmelanoma are also considered to be BCG-responsive cancer (Gutterman et al., 1976, CancerImmunol Immunother 1, 99–107; Kremenovic et al., 2020, J Intern Med, 288, 625–640).“Recurrence” or “cancer recurrence” refers to cancer that has returned (come back) after treatment, usually after a period of time during which the cancer could not be detected, wherein the returning tumour is of the same stage as the initial tumour. The cancer may come back to the same place as the original (primary) tumour or to another place in the body. “Disease worsening” or “disease progression” refers to the occurrence of events that include the appearance of a tumour having a higher stage than the initial tumour, which usually involves the need for the removal of the bladder (cystectomy), systemic chemotherapy, radiation therapy, or other therapies indicative of abandonment of strategies for the treatment of NMIBC. For instance, “disease progression” can be defined as the development of a T2 or greater disease, lymph node or metastatic disease, or receipt of any cystectomy. Recurrence-free survival (RFS) rate is defined as the proportion of patients who survive without any signs or symptoms of cancer recurrence, specifically without developing a tumor of the same stage and grade as the primary tumor. In some instances, RFS rate can be calculated including all recurrences (both low- and high-grade) and any progression events occurring as the first event. RFS rate calculated this way is also referred to as “RFS rates with progression events as the first event” in this description. High-grade recurrence-free survival (High-grade RFS) rates are determined by considering only high-grade recurrences and progression events occurring as the first event. Progression-free survival (PFS) rate is defined as the proportion of patients who survive with the disease without any signs of the cancer worsening, specifically without developing a tumor of a higher stage or grade than the initial tumor. Cancer-specific survival (CSS) rates or cancer-specific free survival (CSS) rates are defined as the proportion of patients who are alive after a specified period of time following a cancer diagnosis, without dying from that specific cancer, in this case bladder cancer. This measure excludes deaths from other causes, focusing solely on mortality directly attributable to the cancer being studied. Event-free survival (EFS) rate is defined as the proportion of patients who have not experienced any negative event (recurrence, progression or death) over a specified period of time after treatment.“Hazard ratio” (abbreviated as “HR”) is a measure used in survival analysis to compare therisk of a certain event happening at any given point in time between two groups. The terms “patient”, “subject”, “human subject”, and “individual” may be used interchangeably in the context of the present invention, and refer to any human being susceptible of being administered the liposome formulation of the present invention. Preferably, the patient is a human who has been diagnosed with cancer, preferably a cancer responsive to BCG treatment, such as bladder cancer, breast cancer and / or melanoma, preferably bladder cancer, and more preferably NMIBC (such as high-risk NMIBC) and even more preferably high-risk T1 NMIBC or high-risk Ta NMIBC, optionally associated to CIS. Unless expressly specified otherwise, the term “comprising” is used in the context of the present application to indicate that further features such as ingredients may optionally be present in addition to the features of the list introduced by “comprising”. It is, however, considered a specific embodiment of the present invention that the term “comprising” encompasses the possibility of no further features being present, i.e. for the purpose of this embodiment “comprising” is to be understood as having the meaning of “consisting of”. As used herein, the term “about” means the indicated value ± 1% of its value, or the term “about” means the indicated value ± 2% of its value, or the term “about” means the indicated value ± 5% of its value, the term “about” means the indicated value ± 10% of its value, or the term “about” means the indicated value ± 20% of its value, or the term “about” means the indicated value ± 30% of its value; preferably the term “about” means exactly the indicated value (± 0%). The terms “treatment” or “therapy” encompass both prophylactic and curative methods of treating disease, since both are directed to the maintenance or restoration of health. Irrespective of the origin of pain, discomfort or incapacity, its relief, by the administration of an appropriate agent, is to be construed as therapy or therapeutic use in the context of the present application. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skilled in the art to which this invention belongs. Methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. ABBREVIATIONS µg microgramAIM Activation-induced markerBCG Bacillus Calmette-GuérinBL BaselineBMI Body Mass IndexBSL2 Biosafety level 2CD137 4-1BB antigenCD25 Surface IL-2 receptor α-chainCD69 Cluster of Differentiation 69CEIm Research Ethics Committee with medicines (for the Spanish Comité ético deinvestigación con medicamentos) CFU Colony forming unitsCIS Carcinoma in situ. Non invasive flat bladder cancercm CentimetersCRF Case Report FormCSS Cancer-specific survival or cancer-specific free survivalCSTD Closed System Transfer DeviceDS Drug substanceEFS Event-free survivalELISA Enzyme-linked immunosorbent assayELISPOT Enzyme-linked immunospot assayEMEA European Medicines AgencyESAT-6 Early Secretory Antigenic Target (6 kD) of M. tuberculosisFCMtb Fragmented cells of M. tuberculosis or Mycobacterium tuberculosis cell wallfragments FIM First in manGCP Good Clinical PracticeGMP Good Manufacturing PracticesHIV Human Immunodeficiency VirusHMtb Harvest from Mtb Expansion cultureHSP16.3 Recombinant 16 kDa protein of M. tuberculosisHR Hazard ratioHUGTiP Hospital Universitari Germans Trias i PujolICF Informed Consent FormICH International Council on HarmonisationICS Intracellular cytokine stainingIEC Independent Ethics CommitteeIFN-γ Interferon gammaIL-2 Interleukin 2IMP Investigational medicinal productIPC In process controlsLCS Liposome concentrate suspensionLMR Lymphocyte-Monocyte RatioLPS LipopolysaccharideLS Liposomal suspensionLTBI Latent tuberculosis infectionMIBC Muscle-invasive bladder cancermL MilliliterMtb Mycobacterium tuberculosisMtb-C Mycobacterium tuberculosis-complexNaCl Sodium ChlorideNK Natural killer cellNLR Neutrophil-Lymphocyte RatioNMIBC Non-muscle invasive bladder cancer°C Degree CelsiusOX40 CD134 antigenPBMCs Peripheral blood mononuclear cellsPFS Progression-free survivalPLR Platelet-Lymphocyte RatioPMA Phorbol 12-myristate 13-acetatePPD Protein-purified derivativeq.s. Quantum sufficitRFS Recurrence-free survivalSAE Serious Adverse EventSEB Staphylococcal enterotoxin BSEM Standard Error of the MeanT1 Tumours invading the lamina propriaT2 Tumours invading the muscle of the bladder wallTa Tumours confined to the epithelial mucosaTB TuberculosisTh1 Type 1 T-helper cellTh2 Type 2 T-helper cellTNF-α Tumour Necrosis FactorTreg Regulatory T cellsTST Tuberculosis skin testTURBT Transurethral resection of bladder tumourUTE Unitat de Tuberculosi Experimentalw / v weight / volumew / w weight / weightW16 Week 16W2 Week 2W6 Week 6WHO World Health OrganizationWSL Working seed lotBRIEF DESCRIPTION OF FIGURES Figure 1: Flow-chart showing the upstream process for the production of the drug substance (FCMtb), including the materials and reagents involved in the process and suitable in-process controls. Figure 2: Flow-chart showing the downstream process for the production of the drug substance (FCMtb), including the materials and reagents involved in the process and suitable in-process controls. Figure 3: Protein characterisation. Figure 3a: SDS-PAGE with Coomassie Blue staining. Lane 1: Molecular weight. Lane 2: Reference FCMtb-81 batch. Lane 3: Reference FCMtb-81 batch. Lane 4: Study FCMtb-83 -20 °C 12 mo stability batch. Lane 5: Study FCMtb-83 -20 °C 12 mo stability batch. Lane 6: Study FCMtb-86 RT 1-month stability batch. Lane 7: Study FCMtb-86 RT 1-mo stability batch. Lane 8: Study FCMtb-8640 °C 1-mo stability batch. Lane 9: Study FCMtb-8640 °C 1-mo stability batch. Lane 10: Molecular weight. Figure 3b: SDS-PAGE Silver staining. Lane 1: Molecular weight. Lane 2: Reference FCMtb-81 batch. Lane 3: Reference FCMtb-81 batch. Lane 4: Study FCMtb-83 -20 °C 12 mo stability batch. Lane 5: Study FCMtb-83 -20 °C 12 mo stability batch. Lane 6: Study FCMtb-86 RT 1-mo stability batch. Lane 7: Study FCMtb-86 RT 1-mo stability batch. Lane 8: Study FCMtb-8640 °C 1-mo stability batch. Lane 9: Study FCMtb-8640 °C 1-mo stability batch. Lane 10: Molecular weight. Figure 3c: Western-Blot analysis for the HSP70, PstS1, 85 complex and HSP16.3 Mycobacterium tuberculosisantigens. Lane 1: Molecular weight. Lane 2: HSP16.3 antigen. Lane 3: 85A antigen. Lane 4: PstS1 antigen. Lane 5: HSP70 antigen. Lane 6: FCMtb-87. Lane 7: FCMtb-87 HMtb. Lane 8: FCMtb-86. Lane 9: FCMtb-86 HMtb. Lane 10: Molecular weight. Figure 4: Lipid analysis. Figure 4a: Trehalose dimycolate TLC analysis. Lane 1: TDM standard. Lane 2: Reference FCMtb-81 batch. Lane 3. Study FCMtb-86 RT 6 mo stability batch. Lane 4. Study FCMtb-8640 °C 6 mo stability batch. Lane 5. Study FCMtb-86 -20 °C 6 mo stability batch. Lane 6: TDM standard. Figure 4b: Mycolic acids TLC analysis. Lane 1: MA standard. Lane 2: Reference FCMtb-81 batch. Lane 3. Study FCMtb-86 RT 6 mo stability batch. Lane 4. Study FCMtb-86 RT 6 mo stability batch. Lane 5. Study FCMtb-8640 °C 6 mo stability batch. Lane 6:Study FCMtb-8640 °C 6 mo stability batch. Lane 7: Study FCMtb-86 -20 °C mo stability batch.Lane 8: Study FCMtb-86 -20 °C 6 mo stability batch. Lane 9:MA standard. Figure 4c:Lipoarabinomannan (LAM) Western-Blot analysis of different FCMtb batches and their corresponding HMtbs. Lane 1: Molecular weight. Lane 2: LAM antigen 0.270 µg. Lane 3: LAM antigen 0.068 µg. Lane 4: LAM antigen 0.017 µg. Lane 5: FCMtb-83 batch. Lane 6: FCMtb-83 HMtb. Lane 7: FCMtb-86 batch. Lane 8: FCMtb-86 HMtb. Lane 9: Molecular weight. LM: Lipomannan. Figure 5: Freeze-fracturing preparation of liposomal concentrate (LCS) bulk (electronic microscopy). Figure 6: Flow-chart of the process according to the preferred mode of the drug product production. Figure 7: Study design showing the timepoints of administration of RUTI or placebo, and later BGC. Figure 8: Schematic representation of patient disposition across different stages of the study. Figure 9: Frequency of CD4+ and CD8+ T cells and their subsets according to the expression of CD27 in peripheral blood at baseline. Frequencies determined in placebo (white bars and black dots) and RUTI (gray bars and white dots) vaccinated patients are represented as percentages of the total CD3+ T cells. Data represent the mean (bars) ± SEM (error bars) and each dot represents a patient and is the average of two independent stainings. Differences were testedusing an unpaired t test. &p ≤ 0.05.Figure 10: Immune evolution of placebo and RUTI vaccinated high-risk NMIBC patients. Changes in the proportions of CD4+, CD4+CD27+, and CD4+CD27- T cells (A) and CD8+, CD8+CD27+, and CD8+CD27- T cells (B) over the course of the study in placebo and RUTI vaccinated patients (white bars and black dots and gray bars and white dots, respectively) in non-stimulated samples and in PPD-stimulated samples (light gray bars and black dots and black bars and white dots, respectively) are shown. Data represent the mean (bars) ± SEM (error bars) and each dot represents a patient and is the average of two independent stainings. Statistically significant differences were calculated using a Wilcoxon’s matched-pair signed rank test between paired samples and a Mann-Whitney U nonparametric test for unpaired samples (differences between samples in placebo and RUTI groups indicated as &). # denotes differences between BL and W2 samples and attributed only to vaccination. *p ≤ 0.05; **p ≤ 0.01. Figure 11: Immune system modulation by RUTI vaccination in high-risk NMIBC patients before BCG intravesical treatment. Fold change values, calculated as differences in the frequency of immune populations in pre- versus post-vaccination (BL and W2 samples, respectively) in placebo and RUTI patients (white bars and black dots and gray bars and white dots, respectively) in non-stimulated samples. Data are presented as box and whiskers (5–95 percentile). Differences were tested using Wilcoxon signed rank test. *p ≤ 0.05. Figure 12: Modulation of the immune response by RUTI administration in high-risk NMIBC patients before BCG intravesical treatment. Fold change values, calculated as differences in the frequency of AIM+ cells (PPD-stimulated condition) in pre- versus post-vaccination (BL and W2 samples, respectively) in placebo and RUTI group (light gray bars and black dots and black bars and white dots, respectively) in CD4+ T cells (A–C) and CD8+ T cells (D–F). Fold changes in the frequency of AIM+ cells in CD27+ and CD27- populations in CD4+ T cells (B–C) and CD8+ T cells (E–F). Data are presented as box and whiskers (5–95 percentile). Differences were tested using a Wilcoxon signed rank nonparametric test (differences compared to 1); *p ≤ 0.05; **p ≤ 0.01. A Mann-Whitney U nonparametric test for unpaired samples was usedto calculate differences between samples in placebo and RUTI groups; &p ≤ 0.05; &&p ≤ 0.01.Figure 13: Evolution of AIM+ CD4+ T cells in specific and polyclonal stimulated samples over time. Frequencies of CD25+ (A), CD69+ (B), CD137+ (C), and OX40+ (D) CD4+ T cells in samples stimulated with BCG, SEB, or PMA+ionomycin over time in placebo and RUTI vaccinated patients. Data represent the mean (bars) ± SEM (error bars) and each dot represents a patient. Statistically significant differences were calculated using a Wilcoxon’s matched-pair signed rank test between paired samples (samples from the same patient; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001) and a Mann-Whitney U nonparametric test for unpaired samples (differencesbetween samples in placebo and RUTI groups; &p ≤ 0.05).Figure 14: Cytokine profile of CD4+ T cells in response to specific and polyclonal stimulation over time. Frequencies of IFN-^+, IL2+, and TNF-^+ CD4+ T cells in samples stimulated with PPD (A), BCG (B), SEB (C), or PMA+ionomycin (D) over time in placebo and RUTI vaccinated patients. Data, given as percentages of the total CD4+ T cells, represent the mean (bars) ± SEM (error bars) and each dot represents a patient. P values were calculated by a paired two-tailed Wilcoxon test for comparisons between time points in the same patient. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001. Figure 15: Overall CD4+ and CD8+ T cell changes and activation-induced markers over timewithout ex vivo stimulation in vaccinated high-risk NMIBC patients during intravesical BCGtreatment. Fold change values were calculated as differences in the frequency of immune populations in pre-vaccination (BL) versus W6 and W16 samples in non-stimulated samples. Changes in CD4+ and CD8+ T cells (A), AIM profile of CD4+CD25+ (B), CD4+CD25+CD27+ (C), and CD4+CD137+ cells (D). Data from placebo patients are depicted in white bars and black dots and data from RUTI patients in gray bars and white dots as box and whiskers (5–95 percentile). Statistically significant differences were calculated using a Wilcoxon signed rank nonparametric test (differences compared to 1; *p ≤ 0.05; **p ≤ 0.01;***p ≤ 0.001), a Wilcoxon matched-pair signed rank non-parametric test between paired samples (samples from the same patient at W6 and W16; *p ≤ 0.05; **p ≤ 0.01 black lines) and a Mann-WhitneyU nonparametric test for unpaired samples (differences between the two cohorts; &p ≤ 0.05;black lines). Figure 16: Antigen-specific CD4+ T cell response over time in vaccinated patients with high- risk NMIBC during intravesical BCG treatment. Fold change values in the frequencies of AIM+(CD25+, CD137+, and OX40+) in CD4+ T cells at W6 and W16 after ex vivo PPD stimulation (A).Fold changes in the expression of CD25+ and CD69+ (B) and expression of CD137+ and OX40+ (C) in CD4+CD27+ and CD4+CD27- T cells at W6 and W16. Data from placebo and RUTI patients is shown as light gray bars and black dots and black bars and white dots, respectively. Data are presented as box and whiskers (5–95 percentile). Statistically significant differences were calculated using a Wilcoxon signed rank non-parametric test (differences compared to 1), a Wilcoxon matched-pair signed rank nonparametric test between paired samples (samples from the same patient at W6 and W16). *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001. Figure 17: Cytokine profiling by intracellular staining over time. Frequencies of individual cytokine (IFN-^+, IL2+, and TNF-^+) (A) and total cytokine expressing (B) CD4+ T cells over time after PPD stimulation. Frequencies of CD4+ T cells producing multiple cytokines (triple and double-positive producing cells) after PPD stimulation (C). Frequencies of individual cytokine (IFN-^+, IL2+, and TNF-^+) (D) and polyfunctional cells (E) after SEB stimulation. Frequencies are given as percentages of the total CD4+ T cells for placebo and RUTI group. Data represent the mean (bars) ± SEM (error bars) and each dot represents a patient. P values were calculated by a paired two-tailed Wilcoxon test for comparisons between time points in the same patient. *p ≤ 0.05; **p ≤ 0.01.Figure 18: M. tuberculosis-specific CD4+ T cell response after RUTI vaccination in BCG-treatedpatients. Frequencies of total cytokine-positive CD4+ T cells (A) and CD8+ T cells (B) at differenttime points after ex vivo HSP16.3 stimulation in placebo and RUTI groups. Frequencies aregiven as percentages of the total CD4+ and CD8+ T cells. Data represent the mean (bars) ± SEM (error bars). Statistically significant differences were calculated using a paired two-tailed Wilcoxon test (comparisons between time points in the same patient; *p ≤ 0.05 ) and a Mann- Whitney U non-parametric test for unpaired samples (differences between the two cohorts;&p ≤ 0.05).Figure 19: Cytokine profile of CD4+ and CD8+ T cells in response to M. tuberculosis-derivedantigens over time. Frequencies of IFN-^+, IL2+, and TNF-^+ CD4+ and CD8+ T cells after stimulation with ESAT-6 (A and C), or HSP16.3 (B and D) in placebo and RUTI vaccinated patients. Data, given as percentages of the total CD4+ and CD8+ T cells, represent the mean (bars) ± SEM (error bars) and each dot represents a patient. P values were calculated by a paired two-tailed Wilcoxon test for comparisons between time points in the same patient (*p ≤ 0.05; **p ≤ 0.01) and by a Mann-Whitney U nonparametric test for unpaired samples(differences between samples in placebo and RUTI groups; &p ≤ 0.05).Figure 20: Kaplan-Meier curves showing results of 3-year follow-up efficacy studies on placebo and on RUTI®-vaccinated patients. Recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and event-free survival (EFS) after a total of 3 years of follow-up are shown for patients who received either placebo or the RUTI® vaccine. Statistical significance was assessed using a log-rank test. Figure 21: RUTI® vaccination strategy efficacy. Swimmer plot illustrating the clinical course and patient response, including the timing of different clinical events, treatments, lost to follow-up, and deaths. Patients with concomitant CIS and those with high-grade T1 (T1HG) are indicated. Figure 22: Kaplan-Meier curves showing results of 5-year follow-up efficacy studies on placebo and on RUTI®-vaccinated patients. Recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and event-free survival (EFS) after a total of 5 years follow- up are shown for patients who received either placebo or the RUTI® vaccine. Statistical significance was assessed using a log-rank test. Figure 23: Kaplan‒Meier curves depicting the 5-year follow-up of placebo- and RUTI- vaccinated patients in the T1 high-grade cohort. Recurrence-free survival (RFS), including both low- and high-grade recurrences; high-grade recurrence-free survival (RFS) considering only high-grade recurrences; progression-free survival (PFS) and cancer-specific survival (CSS) are presented for patients who received either placebo or RUTI vaccine. Hazard ratios and 95% confidence intervals are also provided. Statistical significance was assessed using the log-rank test. DETAILED DESCRIPTION The inventors have surprisingly found that administration of an immunotherapeutic agentbased on cell wall fragments of a virulent strain of Mycobacterium tuberculosis-complex,previously used in the treatment of tuberculosis, is an effective therapeutic agent for the treatment of cancer patients. The agent presented in EP 2090318 B1 and in WO 2023 / 062066 A1 was developed for the treatment of tuberculosis in a prophylactic manner and for the treatment of the active disease, respectively. Nevertheless, the immunological responses elicited by the agent were not known. As such, the efficacy of the agent in the treatment of diseases other than tuberculosis, e.g., cancer, could not have been predicted. Although the agent has been tested in previous clinical studies for the treatment of tuberculosis (EP 2090318 B1 and in WO 2023 / 062066 A1), no suitable preclinical models exist to evaluate anti-cancer efficiency based on cancer recurrence. Hence, no preclinical studies could be performed previous to the clinical study of the present invention. The present invention provides an agent for use in a method of treating cancer. For example,this can be an agent containing fragments from a Mycobacterium tuberculosis-complex foruse in a method of treating cancer, not limited to those particular embodiments disclosed herein. More specifically, the invention provides liposome formulations (drug product) comprisingfragments from a Mycobacterium tuberculosis-complex (MTB-C) strain (Mycobacteriumtuberculosis cell wall fragments, FCMtb, drug substance, as described herein) and a liposome forming agent for use in a method of treating cancer. In several examples of the present invention, the liposome formulation (drug product) is referred to as “RUTI”, or “RUTI®”, as described herein, a particularly preferred embodiment of the liposome formulation of the present invention. This detailed description discloses specific and / or preferred variants of the individual features of the invention. The present invention also considers as particularly preferred embodiments those embodiments, which are generated by combining two or more of the specific and / or preferred variants described for two or more of the features of the present invention. FCMtb (drug substance) can be of any type of substance derived from the MTB-C strain, whereby fragments derived from proteins and / or lipids are preferred. FCMtb within the sense of this application is typically a mixture of different protein antigens and lipids from MTB-C cells. The cell fragments may be obtained by any method known to the person skilled in the art suitable for fragmenting microbial or bacterial cells, such as specifically MTB-C cells, for example homogenisation. The homogenisation can be carried out by means of ultrasound sonication, or by means of the use of small beads of approximately 0.1 mm in diameter, for example, silica or zirconia / silica beads, together with a mechanical homogenizer. As mechanical homogenizer, for example, the BioSpec BeadBeater® model can be used. The MTB-C cells are broken by means of this homogenisation process, so that small cell fragments, typically including nanometre scale cell wall fragments, are obtained. A typically relevant feature of the manufacturing of the cell fragments is the “detoxification” of the cell wall fragments by delipidation, well known to the person skilled in the art, a process that allows removing the endotoxin-like molecules. The FCMtb is therefore preferably detoxified, pasteurized, and lyophilized. As described herein, in a preferred embodiment, the FCMtb refers to cell wall fragments of MTB-C strain NCTC 13536, as described herein and in the examples, e.g., Examples 2 and 3 and Figures 1 and 2. The final drug product, i.e., the liposome formulation of the present invention, most preferably RUTI® as described herein and in the examples, e.g., Examples 1 and 2, is prepared as a liposomal formulation of FCMtb in sucrose, filtered through 0.22 nm. The final drug product, most preferably RUTI, can optionally be lyophilised to facilitate its storage. To that end, the final drug product, most preferably RUTI, can be distributed into vials and lyophilised, for example at a temperature in the range of -45 °C to 25 °C and a pressure between 0.1 and 0.5 mbar, such as 0.150 mbar. In a preferred embodiment, the liposome formulation of thepresent invention comprises the following components: FCMtb as the drug substance and oneor more excipients, preferably selected from sucrose, soy lecithin, sodium cholate, sodium chloride, ethanol and water. In a further preferred embodiment, the liposome formulation of the present invention comprises FCMtb, sucrose, soy lecithin, sodium cholate, sodium chloride, ethanol and water. Table 0 provides the components and amounts per vial comprised in RUTI®. The liposomes or liposomes comprised in the liposome formulation according to this invention usually have a size distribution in which at least 99.9% (by number) are smaller than 1 μm. In a particular embodiment, the z-average size of the particles, as determinable by dynamic light scattering, is 120 nm or less, preferably 110 nm or less, more preferably 95 nm or less, and most preferably 80 nm or less. In dynamic light scattering, the z-average parameter is considered a stable and important number obtainable by the technique, and the size number that is preferably used for quality control purposes. Preferably, the liposomes of the formulation according to this invention are monomodal, i.e., they show only one peak in dynamic light scattering measurements. More preferably, the liposomes of the formulation according to this invention are spherical, as can be tested by electron microscopy of freeze- fracturing preparations of the liposome formulation of the present invention (drug product), as shown in Example 8. Spherical means that for at least 90% of the liposome particles (by number), all surface points of the individual particle have similar or identical distance to the centre of the liposome, i.e., the minimal radius of such a particle relates to the maximal radius of the same particle in a ratio of 0.6 or more, 0.7 or more, 0.8 or more or 0.9 or more. The liposome formulation of the present invention (drug product) according to the present invention can comprise multilamellar or unilamellar liposomes, or a mixture thereof. In line with standard knowledge of the person skilled in the art, the dynamic light scattering measurements should be performed in a suitable buffer, i.e., a buffer which does not by itself cause disruption, disintegration or fusion of the liposomes or significantly destabilize them physically in any other way. As a rule of thumb, any buffer may be suitable as long as both ionic strength and pH value are comparable to the buffer in which the liposomes have been formed may be suitable. Preferably, a buffer of similar or identical composition to the buffer in which the liposomes have been formed, is used. The liposome formulation (drug product) additionally comprises 1 to 20 % (w / v) sucrose, preferably 2 to 12 % (w / v) sucrose, more preferably 3 to 8 % (w / v) sucrose, and most preferably 4 to 6 % (w / v) sucrose. Approximately 5 % sucrose is particularly preferred. It is important to note that, while each of these embodiments relating to different aspects of the invention, the one relating to a particular particle size and the other relating to the presence of sucrose, may be fulfilled individually, these embodiments are not to be seen as mutually exclusive and may well occur in combination. In one particular embodiment, the above-described liposome formulation has a z-average particle size in the range from 40 to 120 nm, preferably from 50 to 100 nm, and more preferably from 55 to 95 nm, and more preferably from 55 to 80 nm. The z-average particle size is thereby preferably measured by dynamic light scattering, as described in general above and in detail in the section “Materials and methods”. In an alternative particular embodiment, the z-average particle size of the above-described liposome formulation may be smaller, so that the liposome formulation is an emulsion, i.e., in this particular embodiment the z-average size of the particles is preferably below 40 nm. In a preferred embodiment of any one or more of the above-described embodiments, the liposomes of the formulation according to this invention are furthermore monodisperse, which means that no significant width of the size distribution is observed. This is technically tested by a low polydispersity index (PDI) as determined by dynamic light scattering, such as 0.400 or less, preferably 0.300 or less. Hence, the liposome formulation is a liposome formulation, wherein the polydispersity Index of the particles as determinable by dynamic light scattering is 0.400 or less, preferably 0.300 or less, and most preferably 0.250 or less.The fragments from the Mycobacterium tuberculosis-complex (MTB-C) strain are obtainableby a process comprising an upstream process and a downstream process. For illustrative purposes, the main steps are briefly described here and particular modes of carrying out the process are given in Examples 2 and 3 below. Upstream process (see, e.g., Example 2): Step 1: Culture of Mtb-working seed lot (WSL)Step 2: Harvest of Mtb-WSL and inoculation and growth of Mtb expansion cultureStep 3: Harvest of Mtb- Expansion culture (HMtb) and freezingDownstream process (see, e.g., Example 3): Step 4: Cell fragmentation and delipidation (purification) Step 5: Pasteurization Step 6: Filtration and filling Step 7: Freeze-drying, encapsulation, and labellingIn a more preferred embodiment, the Mycobacterium tuberculosis-complex (MTB-C) strain isa virulent Mycobacterium tuberculosis-complex (MTB-C) strain. Virulent refers to thepathogenicity by case and / or the ability of the bacilli to invade the tissues of the host. The virulent strain can be any virulent strain of any of the species belonging to MTB-C, but a strainbelonging to M. tuberculosis is preferred. The MTB-C strain NCTC 13536, deposited by ArchivelFarma S.L. in 2010 (December 3, 2010) at the National Collection of Type Cultures (NCTC), London [MI6], UK, is more preferred. The MTB-C strain according to this invention may be cultivated by inoculation in culture media well-known by the person skilled in the art, for example Middlebrook 7H10 or 7H11 agar, Sauton’s medium or Proskauer-Beck medium. The culture of the virulent strain is preferably performed over an extended time period, such as, for example, a period equal to or greater than three weeks, preferably comprised between 3 and 4 weeks. The temperature of the culture is preferably maintained between 34°C and 38°C. Once the culture ends, the cells are harvested and isolated using techniques well known in the art, such as those described in patent application ES2231037-A1. The liposome agent of the liposome formulation (drug product) is preferably a hydrogenated, partially hydrogenated, or non-hydrogenated phospholipid. The phospholipid used can be or comprise, for example: phosphatidylcholine, phosphatidylserine and / or phosphatidylinositol. Most typical is phosphatidylcholine, which can be synthesized or isolated from a variety of natural sources. Preferably, the liposome forming agent is or comprises lecithin, selected from the group consisting of egg lecithin and soy lecithin. Soy lecithin is a complex mixture ofphospholipids including inter alia phosphatidylcholine and is particularly preferred. Typicallipids which may also be comprised in the formulation, either as liposome forming agent, or as further component, are: dicetyl phosphate (DCP), dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), dioleoyl phosphatidylcholine (DOPc), dioleoyl phosphatidylethanolamine (DOPE), dioleoyl phosphatidylserine (DOPS), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG), phosphatidylcholine (PC) and / or phosphatidylserine (PS), whereby the respective lipid may be hydrogenated, partially hydrogenated, or non-hydrogenated. The liposomes can be formed using conventional auxiliary lipids and techniques well-known by the person skilled in the art, such as those described in the patent application ES2231037-A1. It is further preferred that in any one of the embodiments described above, the ratio of (a)the fragments from a Mycobacterium tuberculosis-complex (MTB-C) strain and (b) theliposome forming agent, is between 0.01:1 and 1:1, preferably between 0.06:1 and 0.1:1. In a more preferred embodiment of any of the above-described, the liposome formulation additionally comprises (c) a tensioactive agent. Generally, all types of agents capable of changing the value of surface tension may be used as tensioactive agent in the sense of this invention, but excluded are compounds which fall under the definition of the liposome- forming agent given above. Various types of tensioactive agents are known to the person skilled in the art and may be used in the liposome formulation according to the present invention. As is known to the skilled person, tensioactive agents are generally chemicals with a polar-nonpolar structure. Without wishing to be limited to any particular theory, tensioactive agents generally have the tendency to locate to the surface of particles, thereby creating a monomolecular layer on the interface that reduces the surface tension value. Tensioactive agents are also referred to as surfactants or active surface agents. In a preferred embodiment of the surfactant-containing liposome formulation, the tensioactive agent is selected from sterols and derivatives thereof, such as cholesterol, and / or bile salts or derivatives thereof, such as cholate. Particularly preferred embodiments are those wherein the tensioactive agent is selected from cholate, deoxycholate, cholesterol and cholesterol hemisuccinate. A good, but not limiting mode of carrying out the invention is where the liposomes of the formulation comprise both soy-derived lecithin and sodium cholate. In an even more preferred embodiment, the liposome formulation comprising (c) the tensioactive agent, is a liposome formulation, wherein the ratio between (a) and (c) is between 0.05:1 and 3:5 (w / w). Various types of liposome-forming agents may be used, as are well known to the person skilled in the art. The liposomes can optionally contain additives improving their stability, for example vitamin E, which is believed to act as a lipid antioxidant. In a more preferred embodiment, the liposome formulation described above is a liposome formulation, wherein the fragments of MTB-C cells are or comprise cell wall fragments.Any strain belonging to MTB-C, and preferably any strain belonging to Mycobacteriumtuberculosis, may be used. In another more preferred embodiment, the liposome formulation described above comprises fragments of the MTB-C strain NCTC 13536, which was deposited in 2010 at the NCTC in London (Example 1). Another strain which may be used, and fragments of which may therefore be comprised in the liposome formulation, is H37Rv, which, for example, can be obtained from the National Collection of Type Cultures (NCTC), London, Great Britain (deposit number NC007416) and is often used by researchers in the field. It is also possible that more than one strain be used, i.e., that the liposome formulation comprises fragments of various, such as two, three, or more than three strains.Considering the approximately 4000 putative antigens of M. tuberculosis, it is impossible toanalyse the drug substance for all of these proteins. Nevertheless, certain MTB-C proteins have been shown to be relevant for the desired immune response. These are five proteinbands corresponding to approximate sizes of 6, 10, 16, 30, and 38 kDa (Renshaw, et al., 2005,EMBO Journal 24, 2491-2498; Singh, et al., 2005, Clin. Diagn. Lab. Immunol. 12(2), 354-358;Rodriguez-Hernandez, et al. 2020, Biomed and Biotechnol 21(11):856-870; Meier et al., 2018,Frontiers in Immunology Vol 9 Article 2476). Therefore, in a preferred embodiment, the liposome formulation described above comprises at least two, preferably three, more preferably four, more preferably five, and most preferably all of the following: (i) a first polypeptide having a molecular weight of about 70 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the first polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisHSP70 protein (Rv0350), (ii) a second polypeptide having a molecular weight of about 38 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the second polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis PsTS1 protein (Rv 0934), (iii) a third polypeptides having a molecular weight of about 30–34 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thethird polypeptides have a mass fingerprint similar to a mass fingerprint of M.tuberculosis Ag85 complex including Ag85A and Ag85B proteins (Rv 3804c and Rv 1866c, respectively), (iv) a fourth polypeptide having a molecular weight of about 16 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the fourth polypeptide has a mass fingerprint similar to a mass fingerprint of M.tuberculosis HSP16 protein (Rv 2031c), (v) a fifth polypeptide having a molecular weight of about 10 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the fifth polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisCFP10 protein (Rv3874), and (vi) a sixth polypeptide having a molecular weight of about 6 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the sixth polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisESAT-6 protein (Rv3875). In a more preferred embodiment, the liposome formulation described above comprises at least two, preferably three, more preferably four, more preferably five, and most preferably all of the following: (i) a polypeptide having a molecular weight of about 38 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisPsTS1 protein (Rv 0934), (ii) a polypeptides having a molecular weight of about 30–34 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the polypeptides have a mass fingerprint similar to a mass fingerprint of M. tuberculosis Ag85 complex including Ag85A and Ag85B proteins (Rv 3804c and Rv 1866c, respectively), (iii) a polypeptide having a molecular weight of about 16 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisHSP16 protein (Rv 2031c), (iv) a polypeptide having a molecular weight of about 10 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisCFP10 protein (Rv3874), and (v) a polypeptide having a molecular weight of about 6 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the polypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosisESAT-6 protein (Rv3875). In a yet more preferred embodiment thereof, the liposome formulation further comprises a lipopolypeptide having a molecular weight of about 19 kDa as determined by electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein the lipopolypeptide has a massfingerprint similar to a mass fingerprint of M. tuberculosis 19 kDa lipoprotein antigenprecursor LpqH (Rv 3763). The respective band can be visualized by methods known in the art, such as silver staining. The researchers of the present invention surprisingly found that this polypeptide induces a high total IgG humoral response, which may be the highest humoral response among all antigens in the formulation. Examples of how the polypeptides or lipopolypeptides may be identified are given in Example 4. Even more preferably, the liposome formulation described above is further characterized inthat at least one of the following antigens of Mycobacterium tuberculosis, or fragment thereof, is present: HSP70, PsTS1, 85 complex, HSP16, and most preferably at least one of HSP70, PsTS1, 85 complex, HSP16. Fragment in this sense is any part, such as for example a degradation product, of any of these polypeptides. Various ways of obtaining such fragments are possible, for example chemical or enzymatic hydrolysis, whereby it is not relevant if the fragmentation had occurred purposely or not, prior to liposome formation or thereafter. It is preferred that the respective fragment can be assigned to its respective origin, such as, for example, by substantial overlap in amino acid sequence, such as at least 5, at least 10, at least 20 consecutive amino acids.The drug substance (DS, FCMtb) is manufactured from bacilli grown under the stressfulconditions of starvation, low pO2and low pH, conditions achieved gradually by culturing on solid media and leading to stationary growth in which a slow metabolism makes bacilli more resistant to stress. The multiantigenic nature of DS (multiantigenic protein mixture plus lipids instead of purified antigens alone) appears to be an advantage and, in this sense, fragmentation process is selected to allow the optimal presentation of this cellular antigens’ mixture. As described herein, in a preferred embodiment, the DS (FCMtb) refers to cell wall fragments of MTB-C strain NCTC 13536, as described herein and in the examples, e.g., Examples 2 and 3 and Figures 1 and 2. Another relevant feature of the manufacturing of the drug substance is the delipidation of the cell wall fragments which allows removing the endotoxin like molecules. Under such conditions, cultured bacilli include mainly characteristics of non-replicating bacilli. The antigens present in FCMtb are thus expected to trigger a wide poli-antigenic response against active bacilli and non-replicating bacilli. Further details regarding the production process can be found in the examples. Mycobacterial glycolipids have long been recognized to have immunomodulatory activity, notably the induction of granulomatous responses and to exert potent adjuvant-like effects. Therefore, in a more preferred embodiment, the liposome formulation described abovecontains lipids which are typically found in Mycobacterium tuberculosis, or derivatives thereof, such as conjugation products like sugar-conjugated lipids. Several immunogenic lipidcomponents have been identified in M. tuberculosis samples (Brennan, Tuberculosis(Edinburgh), 2003, 83(1-3), 91-97; Chouldhary et al., 2018, Journal Immunology, 200:3053-3066) and analytical methods for their determination have been developed (electrophoresis, SDS-PAGE, thin layer chromatography, western blot). Although the isolation of each lipid component would require such an aggressive treatment that quantitative data or percentages of each component detectable in the MTB-C extract or in the liposome formulation are difficult to obtain, the qualitative characterisation shall serve to characterize a further preferred embodiment of this invention. According to this further preferred embodiment, one or more of mycolic acids, preferably belonging to any one or more of types I, III, or IV is comprised. Alternatively or in addition, a sugar-conjugated mycolate, preferably trehalose dimycolate may be comprised in the formulation. Alternatively or in addition, a glycolipid lipoarabinomannan (LAM) may be comprised in the formulation. Furthermore, the multiantigenic nature of the fragments (multiantigenic protein mixture plus lipids, instead of purified antigens alone) is believed to be an advantage and therefore the cell fragmentation process can be adapted by the skilled person so as to allow the optimal cellular antigen mixture. Homogenisation of the MTB-C cells is carried out in the presence of one or more surfactants, preferably a nonionic surfactant. Hence, the liposome formulation of the present invention (drug product, preferably RUTI) described above may additionally comprise one or more such surfactants. A large number of such surfactants is within the standard knowledge of a person skilled in the art. Preferably, the nonionic surfactant used is selected from the group consisting of alkylphenol ethoxylates, and sorbitan ester ethoxylates. More preferably, the nonionic surfactant is selected from the group of octylphenol ethoxylates. Even more preferably, octylphenol ethoxylates with an ethylene oxide content comprised between 7 and 8 moles are used; corresponding surfactants can be found on the market under the name Triton X- 100. The homogenised mass containing the cell wall fragments is subjected to a conventional treatment to separate and discard non-fragmented cells and solubilized components. Centrifugation at different speeds and washing with buffer solution as described in patent application ES2231037-A1 can be used for example. Sediment containing the cell wall fragments is obtained after performing the mentioned purification processes. Said sediment is dispersed in phosphate-buffered saline (PBS) buffer and is subjected to a conventional treatment to ensure the complete inactivation of the MTB-C cells which may have remained viable after the fragmentation and purification process. The mentioned treatment can be a chemical process, for example by means of treatment with formaldehyde, or a physical process, for example by means of autoclaving or pasteurisation treatment. Examples of lipid characterization are given in Example 5. In a further preferred embodiment, the above-described liposome formulation additionally comprises one or more salts or solutions thereof, whereby the preferred salt is sodium chloride. In an even more preferred embodiment of any of the above, the liposome formulation is freeze-dried. The liposomes can be subjected to lyophilisation to thus obtain the immunotherapeutic agent in the form of lyophilised liposomes. To that end, the dispersion can be distributed into vials and lyophilised at a low temperature, for example at a temperature in the range of -45 °C to 25 °C temperature and a pressure between 0.1 and 0.5 mbar, such as 0.150 mbar. The vials obtained after lyophilisation contain the liposome formulation suitable as immunotherapeutic agent and they are preferably stored at very low temperatures, for example at 5 °C. The invention also provides a suspension, wherein the liposome formulation of the present invention (drug product, preferably RUTI®) is reconstituted in a solvent. In a preferred embodiment, the solvent of this suspension is aqueous, more preferably and most preferably is or comprises physiological serum. Methods of suspending liposome formulations in a solvent are well known to the person skilled in the art. It is a particularly advantageous property of the formulation according to this invention that it can be suspended faster than conventional liposome formulations comprising MTB-C fragments. One object of the invention is the provision of an agent comprising cell wall fragments of a strain of MTB-C, preferably MTB-C strain NCTC 13536, for the preparation of a pharmaceutical composition, whereby the agent is or comprises the liposome formulation described above in any of the embodiments described or combinations thereof. The main purpose of the pharmaceutical formulation / galenic formulation of the drug substance is to provide a suspension effective and stable enough to be well recognized by immune cells and which has the potential to trigger a relevant cellular immune response in a human or animal body. To that end, the invention also provides a pharmaceutical composition comprising the liposome formulation, or the suspension as described in any one or more of the embodiments described above, and a pharmaceutically acceptable carrier, excipient, or diluent. Various such carriers, excipients, and diluents are known to the person skilled in the art, and they are in no way limited by this disclosure. Rather, any substance suitable as carrier, excipient or diluent may be used. In a preferred embodiment, this pharmaceutical composition additionally comprises a pharmaceutically acceptable adjuvant. Adjuvant is thereby to be understood as a substance comprised in this embodiment of the invention, whereby the adjuvant is a substance capable of stimulating the immune system when applied to a human or animal body in response to the target antigen, whereby the adjuvant does not itself confer immunity. Without wishing to be limited to any particular adjuvant substance, preferred embodiments are wherein the adjuvant is an aluminium salt, such as aluminium chloride, or a mineral oil or a composition comprising mineral oil, such as incomplete Freund’s adjuvant (IFA) or complete Freund’s adjuvant (CFA), or an ammonium halogenide, such as an alkylated ammonium bromide, such as dimethyldioctadecylammonium bromide. It is generally accepted that a liposomation process generates a lipidic environment, facilitating the solubility and leading to a suspension of substances, such as FCMtb (the drug substance of the present invention). Liposomes within the meaning of this invention may be unilamellar, multilamellar, or combinations thereof. The invention also provides a product for use in a method of treatment of the human or animal body by therapy. That is, it provides the liposome formulation according to any one or more of the embodiments described above, the suspension according to any one or more of the embodiments described above, or the pharmaceutical composition according to any one or more of the embodiments described above for use in a method of treatment of the human of animal body by therapy, in particular for the treatment of cancer, preferably a BCG-responsive cancer, e.g., bladder cancer (such as high-risk NMIBC), breast cancer and / or melanoma. The invention thus provides the use of the liposome formulation according to any one or more of the embodiments described above, the suspension according to any one or more of the embodiments described above, or the pharmaceutical composition according to any one or more of the embodiments described above in the preparation of a medicament for the treatment of the human of animal body by therapy, in particular for the treatment of cancer, preferably a BCG-responsive cancer, e.g., bladder cancer (such as high-risk NMIBC), breast cancer and / or melanoma. Hence, the present invention provides a method of treating of the human of animal body by therapy, in particular for the treatment of cancer, preferably a BCG- responsive cancer, e.g., bladder cancer (such as high-risk NMIBC), breast cancer and / or melanoma, wherein the method comprises the administration of the liposome formulation according to any one or more of the embodiments described above, the suspension according to any one or more of the embodiments described above, or the pharmaceutical composition according to any one or more of the embodiments described above to a subject in need thereof. In a preferred embodiment, the cancer is bladder cancer. Preferably, the cancer is NMIBC. In one embodiment, the NMIBC is not low-risk NMIBC. More preferably high-risk NMIBC. Further, it is preferred that the pathological stage is preferably T1 or Ta, optionally associated to CIS. The liposome formulation can be administered parenterally, for example, subcutaneously, intradermally, intramuscularly, intravenously, or intraperitoneally. Parenteral administration such as subcutaneous or intramuscular is preferred. In a particular embodiment, the invention provides this liposome formulation, suspension, or pharmaceutical composition for injection. In a preferred embodiment, the administration is subcutaneous. In another embodiment, the invention provides the liposome formulation, suspension, or pharmaceutical composition of the invention for use in a method of treating cancer in a human subject. In a preferred embodiment, the method of treating cancer is an immunotherapy. In a more preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the present invention is applied in the course of a therapy comprising the treatment with another immunotherapeutic agent (“immunomodulator”). In one embodiment, the liposome formulation is administered to a cancer patient after treatment with another immunomodulator. In a preferred embodiment, the liposome formulation is administered to a cancer patient before treatment with another immunomodulator. “Immunotherapy” in the context of cancer treatment refers to any treatment that modulates an immune response to stimulate the immune system to destroy tumours. The active agent, referred to as “immunomodulator” can be of different origins including, but not limited to, natural, synthetic, or recombinant. Immunotherapy may be performed, for example by means of, but not limited to, therapeutic antibodies, checkpoint inhibitors, T cell transfer therapy, therapeutic cancer vaccines (also known as treatment vaccines), or immune system modulators. Other examples for immunomodulators are interleukins, cytokines, chemokines, immunomodulatory drugs such as immunomodulatory imide drugs, cytosine phosphate-guanosine, oligodeoxynucleotides, or glucans. Immunotherapy may also involve cell-based approaches such as immune cell transplantation, dendritic cell-based pump-priming or vaccination, or adoptive cell transfer, such as T-cell adoptive transfer. Immunomodulators for cancer therapy may also be vaccines, in which case the immunotherapy is referred to as “vaccination”. More specifically, therapeutic cancer vaccines are used to treat a cancer or to prevent its development. Examples for therapeutic cancer vaccines include, but are not limited to cell-based vaccines, protein-based vaccines, peptide- based vaccines, gene-based vaccines, or others. BCG, as defined herein, is a therapeutic cancer vaccine which is based on mycobacterial antigens. It has been the gold-standard treatment for NMIBC associated with high risk of progression or recurrence, see, e.g., Guallar-Garrido S, Julián E. Bacillus Calmette-Guérin (BCG) “Therapy for bladder cancer: an update”, Immunotargets Ther., 2020 Feb 13;9:1-11 or Morales A. “BCG: A throwback from the stone age of vaccines opened the path for bladder cancer immunotherapy”, Can J Urol., 2017 Jun;24(3):8788-8793. It has also successfully been used in the treatment of other BCG-responsive cancers, such as breast cancer and melanoma (Gutterman et al., 1976, CancerImmunol Immunother 1, 99–107; Kremenovic et al., 2020, J Intern Med, 288, 625–640).Without wishing to be bound to theory, BCG immunotherapy induces both local and systemic immune responses but the mode of action by which it acts against tumours is poorly understood. Hence, in one embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is used in a method of treating cancer, preferably a BCG- responsive cancer, e.g., bladder cancer (such as high-risk NMIBC), breast cancer and / or melanoma, more preferably high-risk NMIBC, wherein the treatment further comprises the administration, preferably intravesical, of BCG. Hence, in one embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is used in a method of treating cancer, preferably a BCG-responsive cancer, e.g., bladder cancer (such as high-risk NMIBC), breast cancer and / or melanoma, more preferably high-risk NMIBC, wherein the method comprises the administration, preferably subcutaneous, of the liposome formulation, suspension, or pharmaceutical composition of the invention and the administration, preferably intravesical, of BCG. The administration of the liposome formulation, suspension, or pharmaceutical composition of the invention and BCG may be simultaneous or subsequent. Preferably, the administration is subsequent, i.e., the liposome formulation, suspension, or pharmaceutical composition of the invention is first administered, and after a determined time interval, BCG is administered. The time interval between administration of BCG and the liposome formulation, suspension, or pharmaceutical composition of the invention is preferably from 3 to 30 days, such as from 3 to 10 days, preferably 6 days. In a preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is administered subcutaneously, and the BCG is administered intravesically. In a preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is administered in two doses, one dose is administered after TURBT and the second dose is administered from 5 to 30 days after the first dose, such as from 7 to 28 days after the first dose, preferably from 7 to 10 days after the first dose, more preferably 10 days after the first dose. Preferably, each dose comprises 5–200 μg of FCMtb, preferably 25 µg of FCMtb. Preferably, BCG is also administered in two doses; one dose (the “induction dose”) is administered 3 to 30 days after the last administration of the liposome formulation, suspension, or pharmaceutical composition of the invention, preferably 6 to 15 days after the last administration of the liposome formulation, suspension, or pharmaceutical composition of the invention, even more preferably six days after the last administration of the liposome formulation, suspension, or pharmaceutical composition of the invention. The second BCG dose (the “maintenance course”) is preferably administered in three courses at three, six, and twelve months after the administration of the induction course. Preferably, a BCG dose comprises 2–8 x 108BCG colony forming units (CFU). Hence, in a preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is used in a method of treating high-risk NMIBC, wherein the treatment further comprises the intravesical administration of BCG. Hence, in a preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is used in a method of treating high-risk NMIBC, wherein the method comprises the subcutaneous administration of the liposome formulation, suspension, or pharmaceutical composition of the invention and the intravesical administration of BCG. The administration of the liposome formulation, suspension, or pharmaceutical composition of the invention and BCG is subsequent, i.e., the liposome formulation, suspension, or pharmaceutical composition of the invention is first administered, and after a determined time interval, BCG is administered. The time interval between administration of BCG and the liposome formulation, suspension, or pharmaceutical composition of the invention is preferably 6 days. In a preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is administered in two doses, one dose is administered after TURBT and the second dose is administered from 7 to 10 days after the first dose, preferably 10 days after the first dose. Preferably, each dose comprises 25 µg of FCMtb. Preferably, BCG is also administered in two doses; one dose (the “induction dose”) is administered six days after the last administration of the liposome formulation, suspension, or pharmaceutical composition of the invention. The second BCG dose (the “maintenance course”) is preferably administered in three courses at three, six, and twelve months after the administration of the induction course. Preferably, a BCG dose comprises 2–8 x 108BCG colony forming units (CFU). In a more particular embodiment, the liposome formulation, suspension, or pharmaceutical composition of the invention is used in a method of treating cancer by immunotherapy, wherein the immunotherapy is preferably therapeutic cancer vaccination. In a preferred embodiment, the treatment is a prime-boost vaccination strategy, and, in a more preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the present invention is used as a prime vaccination which is administered prior to treatment with a boost vaccination. In one embodiment, the treatment strategy is homologous prime-boost vaccination, and the boost vaccination is the liposome formulation of the present invention, which is preferably RUTI®. In a preferred embodiment, the treatment strategy is heterologous prime-boost vaccination, i.e., the boost vaccination is not the liposome formulation of the present invention. In a more preferred embodiment of this invention, the boost vaccination isa pharmaceutically active agent derived from an organism from the genus Mycobacteria,preferably, the immunotherapeutic agent is derived from Mycobacterium bovis. In a preferredembodiment, the boost vaccination is BCG, as defined herein. In a more preferred embodiment, prime vaccination with the liposome formulation or pharmaceutical composition of the present invention is followed by BCG vaccination. The inventors of the present invention have found that the formulation or composition according to the present invention is highly effective in the treatment of patients with bladder cancer when it is applied before standard treatment with intravesical BCG. As it was not known what type of immunity would be affected by the liposome formulation or pharmaceutical composition of the present invention (drug product), the inventors first performed different immunological tests to investigate the effects of the drug product alone. Indeed, the inventors were able to associate administration of the drug product with an increase in specific effector CD4+ and CD8+ T cells co-expressing activation-induced markers 6 days after administration of a second dose of the agent compared to placebo. This increase in drug product-specific CD4+ and CD8+ T cells was maintained over time. When used as prime in a prime-boost strategy in cancer therapy, treatment with the liposome formulation or pharmaceutical composition of the present invention (drug product) could halt the activation and increase in regulatory T cells (Tregs, defined as CD4+CD25+CD27+) induced by the boost vaccination (BCG). Vaccination with the liposome formulation or pharmaceutical composition of the present invention could thus be associated with a more balanced, effective, durable, and polyfunctional specific response compared to a placebo control. As shown in the Examples, RUTI® effectively primed a systemic BCG-specific immune response, increasing heterogeneous PPD-specific CD4+ and CD8+ T cells prior intravesical BCG. The data indicate that RUTI® prevents BCG-induced Treg expansion, potentially improving efficacy. RUTI® also generated a broader, more polyfunctional T cell response, with elevated polyfunctional T cells through BCG maintenance. In addition, RUTI® primes the immune system, enhancing systemic BCG-specific responses and potentially improving bladder immune infiltration. Non-vaccinated patients showed a skewed response with CD4+CD25+ upregulation but limited antigen-specific T cell activation, suggesting a weaker local response. Furthermore, the use of the liposome formulation of the present invention (drug product) as prime in a prime-boost strategy in cancer therapy resulted in the prolongation of the time to recurrence. More precisely, for patients who had received both the liposome formulation (drug product) and the boost vaccination and experienced recurrence after 3-years of follow- up, average time to recurrence was 20.32 months on average, whereas for patients from the control group, who had received only the boost vaccination, the average time to recurrence was 4.72 months. Moreover, follow-up efficacy studies demonstrated higher RFS, higher PFS, higher EFS, and higher CSS after TURBT in patients treated with the liposomal formulation of the present invention, as described herein, preferably RUTI®, compared to placebo over a period of five years. Such an efficacy could not have been expected given the small study size (n=40 patients). Hence, in one embodiment, the present invention provides the liposomal formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, wherein the cancer is preferably a BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, even more preferably NMIBC. In one embodiment, the NMIBC is not low-risk NMIBC. Hence, preferably, the NMIBC is high-risk NMIBC, such as NMIBC T1 stage or NMIBC Ta stage, optionally associated to CIS. Therefore, the human subject to be treated with the liposomal formulation or pharmaceutical composition of the present invention is a human subject suffering cancer, preferably a BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, even more preferably NMIBC. In one embodiment, the subject has is high-risk NMIBC, such as NMIBC T1 stage or NMIBC Ta stage. It is preferred that the human subject suffering from NMIBC has primary histological confirmed T1 and / or high- risk tumours and / or CIS. In a preferred embodiment, the human subject has undergone tumour resection before treatment with the liposomal formulation or pharmaceutical composition of the present invention. For instance, it is preferred that the human subject has undergone transurethral resection of bladder tumour (TURBT) before treatment with the liposomal formulation or pharmaceutical composition of the present invention. In a preferred embodiment, the human subject is suitable to be treated with BCG. The delay of recurrence and the resulting greater RFS, PFS and PFS provide a prolonged time window in which milder therapies can be applied, which can be crucial for therapeutic success. A prolongation of PFS has been associated with a better overall efficacy, survival, reduced side effects, and reduced economical costs, for example. Moreover, it could not have been predicted that the agent would improve the efficacy of BCG treatment in bladder cancer patients. This is because the mechanisms by which BCG stimulates the immunological response to act against the tumour are not understood. The enhancement of the BCG effect by the liposome formulation was particularly unexpected since the agent was applied systemically, not intratumourally and / or intravesically like BCG. Hence, more particularly, the enhancing effect of BCG by the agent could not have been predicted. The liposome formulation (drug product) can be administered in a method of treating cancer. The cancer can be of different types such as bladder cancer, melanoma and breast cancer. In one embodiment, the cancer is melanoma. In an alternative embodiment, the cancer is breast cancer. In a preferred embodiment, the cancer in bladder cancer, more preferably NMIBC, more preferably high-risk NMIBC. In a more preferred embodiment, the cancer classifies as T1 or as high-risk tumour. When the liposome formulation or pharmaceutical composition of the present invention is applied in a prime-boost strategy with BCG according to what is described above, BCG may be administered to patients by different routes, depending, for example, on the nature of the cancer. In one embodiment, the route of administration of BCG is injection. In a more particular embodiment, the injection is intratumoral (also referred to as “intralesional”). In a preferred embodiment, BCG is administered to patients via intratumoral injection. In a more preferred embodiment, BCG is administered to bladder cancer patients via intravesical injection (intravesically). In the context of the present invention, the liposome formulation or pharmaceutical composition is to be used in human subjects for the treatment of cancer, more preferably of cancer patients who are additionally treated with a further immunotherapy, such as BCG. In a preferred embodiment, the liposome formulation or pharmaceutical composition of the present invention is administered before treatment with BCG. In a more preferred embodiment, the last dose of the liposome formulation or pharmaceutical composition is administered 3 to 30 days before the day of the first treatment with BCG, preferably 6 to 15 days, most preferably six days before the day of the first treatment with BCG. The dose of BCG depends on the treatment strategy, the route of administration, and on the type of cancer, among others. In one embodiment, BCG is administered weekly over six weeks (corresponding to six applications in total) (induction course). In other embodiment, BCG is further administered weekly over three weeks at 3, 6, and 12 months after the induction course (maintenance course), as described herein. Cancer immunotherapy by BCG is well known to the person skilled in the art and can be administered to human subjects accordingly in the context of the present invention. The dose, route, and timing of administration depend on the type of cancer. BCG can be administered to the patient once or more times. In a particular embodiment of the present invention, BCG is administered to the patient more than once. As described herein, in a preferred embodiment, BCG is administered to the patient in two courses, wherein a second course follows the first course after an adequate length of time. In a more particular embodiment, the courses can be 1) an initial induction course and 2) a maintenance course. In an alternative embodiment, the courses can be 1) an initial induction course and 2) a second induction course. In a more preferred embodiment, the initial induction course consists of weekly administration of BCG over six weeks (corresponding to six applications in total) and is optionally (and preferably) followed by a maintenance course, which consists of three courses of weekly BCG, each for three weeks, wherein each course starts at 3, 6 and 12 months after the induction course, respectively. Preferably, BCG is administered intravesically. In a particular embodiment, in which BCG is intravesically applied, the preferred dose of BCG is 2–8 x 108colony forming units (CFU), optionally diluted in 50 mL sterile solution. A dose of 2–8 x 108CFU of BCG is the most preferred embodiment. Hence, it is preferred that BCG is intravesically applied, once a week for a period of six weeks, wherein each dose comprises 2– 8 x 108CFU of BCG optionally diluted in 50 mL sterile solution. The liposome formulation of the present invention (drug product, preferably RUTI®) or pharmaceutical composition of the present invention can be administered in a method of treating cancer at different therapeutical stages. In one embodiment, the liposome formulation is administered following resection of the tumour. In a more particular embodiment where the cancer is bladder cancer, all visible papillary tumours have been completely resected. Bladder cancer is surgically removed by transurethral resection of bladder tumour (TURBT). In a preferred embodiment, the treatment according to what is described above is administered following TURBT. Hence, in one embodiment, the first dose of the formulation of the present invention (drug product, preferably RUTI®) or pharmaceutical composition of the present invention is administered to a patient, as described above, following TURBT. The suitable dose of the liposome formulation, suspension, or pharmaceutical composition according to what is described above in relation to the use thereof in a method of treatment of the human body by therapy depends on several parameters, including, but not limited to, the method of administration, the cancer, and the subject to be treated. In a preferred embodiment, it is for administration to the human body. In a preferred embodiment thereof, this occurs in a dose comprising 1 to 1000 µg / dose, preferably 3 to 250 µg / dose FCMtb.25 µg of FCMtb per dose is particularly preferred in humans. Hence, preferably, the dosage of the liposome formulation of the present invention comprises 25 μg of FCMtb, as defined herein. Therefore, in a preferred embodiment, the human subject to be treated receives two doses of 25 μg of FCMtb each dose, preferably separated by 10 days between each dose. In the most preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the present invention, which is used in the methods described herein, is RUTI®,which components per vial are described in Table 0. Hence, RUTI® comprises cell wallfragments of Mycobacterium tuberculosis strain NCTC 13536, as described in the Examples(e.g., Examples 1-3). Hence, in the most preferred embodiment, the liposome formulation, suspension, or pharmaceutical composition of the present invention comprises cell wallfragments of Mycobacterium tuberculosis strain NCTC 13536, preferably from 5–200 μg,preferably 25 µg cell wall fragments of Mycobacterium tuberculosis strain NCTC 13536.The liposome formulation or pharmaceutical composition for the use in a method of treating cancer can be administered in the form of a single dose or of several, such as two, three, four, five, or more than five doses, by means of repetition at certain time intervals. Preferably, the liposome formulation or pharmaceutical composition can be administered once or twice in a dose according to what is described above. Most preferably, when the liposome formulation or pharmaceutical composition is administered to patients twice, the second dose is administered 5-30 days after the first dose, such as 7-28 days after the first dose, or 6 to 28 days after the first dose, preferably 10 days, most preferably seven to ten days after the administration of the first dose. In one preferred embodiment, the liposome formulation or pharmaceutical composition of the present invention is administered to patients twice; the first dose is administered after TURBT and the second dose is administered from 7 to 10 days after the administration of the first dose, preferably 10 days after the administration of the first dose. Hence, in one embodiment, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in the treatment of cancer, preferably BCG-responsive cancer, such as bladder cancer in human subjects, more preferably in human subjects treated with TURBT, diagnosed with high-risk NMIBC, wherein the treatment comprises: a. The administration of the liposome formulation or pharmaceutical compositionof the present invention, preferably RUTI®, after TURBT; b. The administration, 3 to 30 days after the administration of liposomeformulation or pharmaceutical composition of the present invention as defined in a., preferably 6 to 15 days after the administration of liposome formulation or pharmaceutical composition of the present invention as defined in a., most preferably six days after the administration of liposome formulation of the present invention as defined in a., of BCG, as defined herein. In a preferred embodiment, BCG in step b. above is administered weekly for six weeks. Preferably, BCG is administered intravesically. Preferably each dose of BCG comprises 2–8 x 108colony forming units (CFU), optionally diluted in 50 mL sterile solution. In a more preferred embodiment, each dose of BCG comprises 2–8 x 108CFU. In a preferred embodiment, the liposome formulation of the present invention, preferably RUTI® in step a. above is administered twice before the administration of BCG as described in b. above. Preferably, the liposome formulation of the present invention, preferably RUTI® in step a. above is administered twice; one time at day 0 and a second time at day 10. Hence, in a preferred embodiment, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in the treatment of cancer, preferably BCG-responsive cancer, such as bladder cancer in human subjects, more preferably in human subjects treated with TURBT, diagnosed with high-risk NMIBC, wherein the treatment comprises: a. The administration of the liposome formulation or pharmaceutical compositionof the present invention, preferably RUTI®, after TURBT, twice, one time at day 0 and a second time at day 10; b. The administration, 3 to 30 days after the administration of liposomeformulation or pharmaceutical composition of the present invention as defined in a., preferably 6 to 15 days after the administration of liposome formulation or pharmaceutical composition of the present invention as defined in a., most preferably six days after the administration of liposome formulation or pharmaceutical composition of the present invention as defined in a., of BCG, as defined herein, wherein BCG is administered weekly for six weeks. Hence, in one embodiment, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in the treatment of cancer, preferably BCG-responsive cancer, such as bladder cancer in human subjects, more preferably in human subjects treated with TURBT, diagnosed with high-risk NMIBC, wherein the treatment comprises: a. The administration of the liposome formulation or pharmaceutical compositionof the present invention, preferably RUTI®, after TURBT;b. The administration, 3 to 30 days after the administration of the liposomeformulation or pharmaceutical composition of the present invention as defined in a., preferably 6 to 15 days after the administration of liposome formulation of the present invention as defined in a., most preferably six days after the administration of liposome formulation or pharmaceutical composition of the present invention as defined in a., of an initial induction course of BCG, as defined herein; and c. The administration of a maintenance course of BCG.In a preferred embodiment, the liposome formulation or pharmaceutical composition of the present invention, preferably RUTI® in step a. above is administered twice before the administration of BCG as described in b. above. Preferably, the liposome formulation or pharmaceutical composition of the present invention, preferably RUTI® in step a. above is administered twice; one time at day 0 and a second time at day 10. Preferably, BCG in each of the administration courses (b. and / or c. above) is administered intravesically. Preferably each dose of BCG (in each one of b. and / or c. above) comprises 2–8 x 108colony forming units (CFU), optionally diluted in 50 mL sterile saline solution. In a preferred embodiment, BCG in step b. above is administered weekly for six weeks. Preferably, the maintenance course as described in c. comprises administering BCG three times in weekly intervals, preferably for three weeks at 3, 6, and 12 months after the induction course (step b. above). The liposome formulation of the present invention (drug product) or pharmaceutical composition of the present invention may be used in a method of treating cancer in a human subject, preferably BCG-responsive cancer, according to as described herein in the absence of any additional treatment. In an alternative embodiment, the drug product or pharmaceutical composition may be used in a method of treating cancer in a human subject, preferably BCG- responsive cancer, according to as described herein in parallel, before, or after other cancer treatments known to the person skilled in the art which comprise radiotherapy, chemotherapy, surgery, and immunotherapy. The present invention provides a liposome formulation or pharmaceutical composition as defined herein (preferably RUT®) for use in a method of treating cancer in a human subject, preferably bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment increases or extends the time to recurrence (average time to recurrence observed for a clinical study group) as compared with the time to recurrence in human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). In a preferred embodiment, the treatment increases or extends the time to recurrence preferably at three years’ time from treatment initiation by a factor of at least two, preferably by a factor of at least three, even more preferably by a factor of at least four, as compared with the time to recurrence in human subjects not treated with the liposome formulation of the present invention (control or placebo group). In one embodiment, the present invention provides a liposome formulation or pharmaceutical composition as defined herein (preferably RUT®) for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment extends or increases the time to recurrence at three years’ time from treatment initiation by one to 20 months, by nine months, preferably by 15 months, more preferably by 15.6 months, or more, as compared with the time to recurrence in human subjects not treated with the liposome formulation of the present invention (control or placebo group). In one preferred embodiment, the present invention provides a liposome formulation or pharmaceutical composition as defined herein (preferably RUT®) for use in a method of treating cancer in a human subject, as described herein, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the mean time to recurrence in the human subject after treatment with the liposomal formulation or pharmaceutical composition of the present invention, preferably at three years’ time from treatment initiation, is more than 4 months, more than 5 months, more than 7 months, more than 10 months, more than 13 months, such as 13.1 months, more than 15 months, or preferably more than 20 months, such as 20.32 months. Preferably, treatment initiation is defined as the time point of TURBT. In one embodiment, the treatment with the liposomal formulation or pharmaceutical composition of the present invention, as described herein (preferably RUT®), is associated with a higher recurrence-free survival (RFS) rate, a higher progression-free survival (PFS) rate, a higher cancer-specific free survival (CSS) rate, and / or a higher event-free survival rate as compared with the the rates of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). In a more particular embodiment, the treatment with the liposomal formulation or pharmaceutical composition of the present invention, as described herein, is associated with a higher recurrence-free survival (RFS) rate, progression-free survival (PFS) rate, cancer-specific free survival (CSS) rate, and / or event-free survival rate as compared with the rate of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group) after 3 years from the initiation of the treatment and / or after 5 years from the initiation of the treatment, preferably after 5 years from the initiation of the treatment. Preferably, the initiation of the treatment is defined as the time point of TURBT. Hence, the present invention provides a liposome formulation or pharmaceutical composition as described herein (preferably RUT®) for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment increases or extends the recurrence-free survival (RFS) rate, progression-free survival (PFS) rate, cancer-specific free survival (CSS) rate, and / or event-free survival rate as compared with the rates of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group) after 3 years from the initiation of the treatment and / or after 5 years from the initiation of the treatment, preferably after 5 years from the initiation of the treatment. Preferably, the initiation of the treatment is defined as the time point of TURBT. Hence, in one embodiment, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject wherein the treatment results in less than 10%, such as less than 5%, or less than 2%, or 0% of progression to muscle-invasive disease (T2 or greater). In one preferred embodiment, the treatment with the liposomal formulation or pharmaceutical composition of the present invention, as described herein, is associated with a recurrence-free survival (RFS) rate of at least 84%, preferably of at least 89%, more preferably of 89.5%, wherein the RFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Hence, the present invention provides a liposome formulation or pharmaceutical composition as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer, and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment is associated with a recurrence-free survival (RFS) rate of at least 73%, such as at least 75%, or at least 80%, or at least 84%, preferably of at least 85%, or at least 89%, more preferably of 89.5%, wherein the RFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. In one embodiment, if calculated including all recurrences (both low- and high-grade) and any progression events occurring as the first event, the treatment with the liposome formulation or pharmaceutical composition as described herein, preferably RUTI®, is associated with a RFS rate of more than 56%, such as more than 60%, or more than 70%, or more than 75%, preferably more than 78%, such as 78.9%. Hence, in one embodiment, the present invention provides a liposome formulation or pharmaceutical composition as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer, and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment is associated with a RFS rate of more than 56%, such as more than 60%, or more than 70%, or more than 75%, preferably more than 78%, such as 78.9%, wherein the RFS rate is calculated including all recurrences (both low- and high-grade) and any progression events occurring as the first event and wherein the RFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Hence, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high- risk NMIBC) in a human subject wherein the treatment results in an recurrence-free survival (RFS) rate of more than 73%, such as more than 75%, or more than 80%, or more than 84%, such as more than 85%, or more than 89%, preferably of 89.5%. In another preferred embodiment, the treatment with the liposomal formulation of the present invention, preferably RUTI®, as described herein, is associated with a progression-free survival (PFS) rate of at least 80%, preferably of at least 90%, more preferably of 100%, wherein the PFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Hence, the present invention provides a liposome formulation or pharmaceutical composition as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG- responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment is associated with a progression-free survival (PFS) rate of at least 73%, such as at least 75%, or at least 80%, preferably of at least 90%, or at least 95%, more preferably of 100%, wherein the PFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Hence, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high- risk NMIBC) in a human subject wherein the treatment results in a progression-free survival (PFS) of more than 73%, such as more than 75%, or more than 78%, such as more than 80%, or more than 85%, or more than 90%, or more than 95%, preferably of 100%. In another preferred embodiment, the treatment with the liposomal formulation of the present invention, as described herein, is associated with a cancer-specific free survival (CSS) rate of at least 90%, preferably of 100%, wherein the CSS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Hence, the present invention provides a liposome formulation or pharmaceutical composition as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment is associated with a cancer-specific free survival (CSS) rate of at least 84%, such as at least 85%, or at least 90%, or at least 95%, or at least 99%, preferably of 100%, wherein the CSS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Hence, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high- risk NMIBC) in a human subject wherein the treatment results in a cancer-specific free survival (CSS) rate of more than 84%, such as more than 85%, or more than 90%, such as more than 95%, or more than 97%, preferably of 100%. In another preferred embodiment, the treatment with the liposomal formulation of the present invention, as described herein, is associated with an event-free survival (EFS) rate of at least 73%, or at least 80%, preferably of at least 89%, more preferably of 89.5%, wherein the EFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Optionally, the hazard ratio associated to the EFS is below 0.4, or below 0.3, preferably it is 0.2 (for the treatment group). Hence, the present invention provides a liposome formulation or pharmaceutical composition as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment is associated with an event- free survival (EFS) rate of more than 50%, such as at least 60%, or at least 65%, or at least 70%, or at least 73%, or at least 80%, or at least 85%, preferably of at least 89%, more preferably of 89.5%, wherein the EFS rate is determined after 3 years from treatment initiation and / or after 5 years from treatment initiation, preferably after 5 years from treatment initiation. Preferably, treatment initiation is defined as the time point of TURBT. Optionally, the hazard ratio associated to the EFS is below 0.4, or below 0.3, preferably it is 0.2 (for the treatment group). Hence, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high- risk NMIBC) in a human subject wherein the treatment results in an event-free survival (EFS) rate of more than 50%, such as more than 60%, or more than 70%, such as more than 73%, such as more than 75%, or more than 80%, or more than 85%, such as at least 89%, preferably of 89.5%. In one embodiment, the treatment with the liposomal formulation of the present invention, as described herein, is associated with higher high-grade recurrence-free survival (RFS) as compared with the RFS of human subjects not treated with the liposome formulation of the present invention (control or placebo group; see Figure 20, Figure 21, Table 9-a, Table 11). Hence, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment increases RFS as compared with the RFS of human subjects not treated with the liposome formulation of the present invention (control or placebo group). In one embodiment, the treatment with the liposomal formulation of the present invention, as described herein, is associated with higher progression-free survival (PFS) as compared with the PFS of human subjects not treated with the liposome formulation of the present invention (control or placebo group; see Figure 20, Figure 21, Table 9-a, Table 11). Hence, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment increases PFS as compared with the PFS of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). In one embodiment, the treatment with the liposomal formulation or pharmaceutical composition of the present invention, as described herein, is associated with higher event- free survival (EFS) as compared with the EFS of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group; see Figure 20, Figure 21, Table 8-a, Table 10). Hence, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment increases EFS as compared with the EFS of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). In one embodiment, the treatment with the liposomal formulation or pharmaceutical composition of the present invention, as described herein, is associated with higher cancer- specific free survival (CSS) as compared with the CSS of human subjects not treated with the liposome formulation of the present invention (control or placebo group; see Figure 20, Figure 21, Table 9-a, Table 11). Hence, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, preferably BCG-responsive cancer, such as bladder cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment increases CSS as compared with the CSS of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). Further, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, as described herein, preferably BCG-responsive cancer, such as cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment results in lower number of recurrence and progression events as compared with the number of recurrence and progression events in human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). Further, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, as described herein, preferably BCG-responsive cancer, such as cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment results in a lower number of cancer-associated deaths as compared with the number of cancer-associated deaths of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). Further, the present invention provides a liposome formulation or pharmaceutical composition, as described herein, preferably RUTI®, for use in a method of treating cancer in a human subject, as described herein, preferably BCG-responsive cancer, such as cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, as described herein, wherein the treatment results in a lower number of recurrence and progression events and cancer- associated deaths as compared with the number of recurrence and progression events and cancer-associated deaths of human subjects not treated with the liposome formulation or pharmaceutical composition of the present invention (control or placebo group). In another embodiment, the present invention provides the liposome formulation or pharmaceutical composition of the present invention for use in a method of treating cancer in a human subject, as described herein, preferably BCG-responsive cancer, such as cancer, breast cancer and / or melanoma, more preferably bladder cancer, and even more preferably NMIBC (such as high-risk NMIBC) in a human subject, wherein the treatment results in an extended time to recurrence, wherein optionally, the time to recurrence is defined as the average time to recurrence observed for a clinical study group, wherein optionally, the time to recurrence is extended compared to an untreated control group, wherein optionally, (i) the time to recurrence is extended by a factor of at least two, preferably the time to recurrence is extended by a factor of at least three, or (ii) the time to recurrence is extended by at least any one of one to nine months, preferably by nine months of by fifteen months, more preferably by nine months. Example 12 shows that no significant safety concerns were observed when RUTI® (the liposomal formulation of the present invention) was administered to cancer patients, in particular to NMBIC patients following TURBT. Additional objects, advantages and features of the invention will become apparent to those skilled in the art upon examination of the description or may be learned by practice of the invention. The following examples and drawings are provided by way of illustration, and they are not intended to be limiting of the present invention. MATERIALS AND METHODS Reference materials a) Monoclonal antibodies: Specific monoclonal antibodies (anti-HSP70, anti-PSTS1, anti- HSP-16.3, (Lionex Diagnostic GmbH, Braunschweig, Germany)) are used for the identification of the protein profile of FCMtb batches. b) Albumin Standard: This standard, used for the determination of protein content, is composed of bovine albumin in 0.9% saline solution (2 mg / mL), conserved in sodium azide (Pierce).c) Trehalose 6,6’-dimicolate from Mycobacterium tuberculosis (TDM) standard: Commerciallyavailable TDM (Sigma) is used for the identification of TDM of FCMtb batches.d) Mycolic acids from Mycobacterium tuberculosis standard: A commercially available mycolicacid (Sigma) is used for the identification of mycolic acid of FCMtb batches. e) Molecular weight marker: A commercially available molecular weight marker named SeeBlue Plus pre-stained Standard (Invitrogen) is used. Determination of parameters a) pH The pH of the reconstituted suspension of the drug substance (FCMtb) (20 mg / mL) is determined by potentiometry according to Ph.Eur.2.2.3 and USP<791>. b) Water content The test for the determination of residual water of the lyophilized FCMtb is carried out using Coulometric Karl Fisher equipment, and it follows the general indications of the Ph. Eur., method 2.5.12, and USP <921> Water determination. c) Determination of total protein content The test for the determination of total protein content of the FCMtb is carried out using a commercial kit (BCA kit, Pierce) and following Ph.Eur., method 2.5.33, method 4 (Bicinchoninic acid or BCA assay) and USP <1057>. d) Identification of protein profile by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) The test is performed according to Ph. Eur., method 2.2.31 and USP <726>; the detection of proteins in the gel is performed by an adapted Coomassie staining or by Silver staining. Test samples: Reconstituted FCMtb in purified water at 40 or 20 mg / mL concentration. Reference solutions: Molecular weight marker, Purified antigens, FCMtb reference standard. Table 1: Reference antigens Purified Antigens M. tuberculosis HSP70 protein (Rv 0350) M. tuberculosis PsTS1 protein (Rv0934) M. tuberculosis Ag85 complex (Ag85 B and Ag85B) proteins (Rv1886c and Rv 3804c) M. tuberculosis HSP-16.3 protein (Rv2031c) M. tuberculosis 19 kDa protein (Rv 3763) M. tuberculosis CFP10 protein (Rv3874) M. tuberculosis ESAT6 protein (Rv3875) For Coomassie staining, Gel-Code Blue Stain reagent solution (Pierce) is used according to the manufacturer’s instructions. For Silver Staining, the PROTSIL1 Kit from Invitrogen is used according to the manufacturer’s instructions. For Western Blot analysis, proteins are separated by SDS-PAGE according to standard methods known in the art and then electrophoretically transferred onto a PVDF membrane for immunodetection using specific monoclonal antibodies. The resulting antigen-antibody complex is visualized by incubation with a secondary antibody labelled with an alkaline phosphatase enzyme. Antigens fromLionex (Braunschweig, Germany) (M. tuberculosis HSP70 protein (70 kDa), M. tuberculosisPsTS1 protein (38 kDa), M. tuberculosis 85 complex (30-34 kDa), and specific monoclonalantibodies anti-HSP70, anti-PsTS1, anti-HSP-16.3, and anti-Ag85B from Lionex are used. e) Identification of mycolic acids Mycolic acids in FCMtb are examined by one-dimensional TLC, following the Ph. Eur., method 2.2.27. Test samples: Lyophilised FCMtb, 20 mg. Reference solutions: Mycolic acid standard (Sigma). Procedure: i) Extraction process: The sample is extracted with chloroform:methanol (1:1)and then it is incubated overnight. The supernatant fraction is kept in reserve for the identification of trehalose 6,6’-dimycolate (TDM). ii) Mycolic acid esterification: 2 mL of methanol:toluene:sulphuric acid (30:15:1;vol / vol) is added to each tube, and esterification is achieved overnight. Then, 2 mL n-hexane is added. The supernatant is recovered in a new tube, and 2 mL n-hexane is added to the sample again. The organic phases are combined and the solvents are evaporated. Then, it is dried under nitrogen flow and it is resuspended with 500 µL hexane. iii) TLC: 20 µL sample is applied three times on a line parallel to the edge of theplate (Silica gel 60 (20x20 cm) (Merck). The chromatographic separation is performed in a saturated tank with a mobile phase (ethylic ether: n-hexane (15:85, vol / vol)). Then, the plate is allowed to dry in air. iv) Mycolic acids are revealed by spraying the plates with a solution ofphosphomolybdic acid in 96° ethanol and heating at 120 °C for 10 min. Mycolic acids in FCMtb samples are determined by comparison with a mycolic acid commercial standard spot. Results are expressed as qualitative data (presence (positive) / absence (negative) of mycolic acid assessed. f) Identification of Trehalose 6,6’-dimycolate (TDM): Test samples: Lyophilised FCMtb, 20–40 mg. Reference solutions: TDM standard (Sigma). Procedures:i) Extraction process: The sample is extracted with chloroform:methanol (1:1;vol / vol) and then it is incubated overnight. The supernatant fraction is dried under nitrogen flow and it is weighted. Finally, dried supernatants are resuspended in chloroform to obtain 40 mg / mL final concentration. ii) TLC: 10 mL extract is applied on a line parallel to the edge of the plate (Silica gel60 (20x20 cm) (Merck). The chromatographic separation is performed in a saturated tank with a mobile phase (chloroform:methanol:water (60:12:1; vol / vol). Then, the plate is allowed to dry in air. iii) Detection: The TDM is revealed by spraying the plates with a solution ofanthrone 1% in sulphuric acid and heating at 120 °C for 5 minutes. iv) Identification: TDM content of FCMtb samples is determined by comparisonwith commercial TDM which is used to generate a standard spot. Results are expressed as qualitative data, i.e., presence (positive) / absence (negative) of TDM assessed. g) Identification of lipoarabinomannan (LAM): For Western Blot analysis of LAM, compounds are separated by SDS-PAGE according to standard methods and then electrophoretically transferred onto a nitrocellulose membrane for immunodetection using specific antibody CS35. The resulting antigen-antibody complex is visualized by incubation with a secondary antibody (IgG Goat anti-mouse IR Dye 800 CW) labelled with an enzyme which catalyses phosphatase alkaline reaction. h) Sterility All processes which require sterility, according to the knowledge of the person skilled in the art, are carried out under sterile conditions; this also applies if sterility is not explicitly mentioned for any given step which requires the same. Sterility test is assessed as prescribed in Ph. Eur.2.6.1 (USP <71>). i) Mycobacteria inactivation The inactivation of mycobacteria is assessed in accordance with Ph. Eur.2.6.2 j) Bacterial endotoxins The test for bacterial endotoxins (LAL test, Limulus Amoebocyte Lysate) is performed according to the general indications of the Ph. Eur., method 2.6.14, following Method D (Chromogenic kinetic method) as well as USP <85>. Fragmentation of bacilli The choice of fragmentation of the bacilli is thought to allow optimal presentation of cell antigens, particularly cell wall antigens. Fragmentation of the FCMtb (drug substance) is determined by both Dynamic Light Scattering (as described below and Laser diffraction methodologies. Laser diffraction allows measuring the fragmentation in a range between 0.04 μm and 2000 µm. The assay is carried out in the Servicios Científico-Técnicos de la Universitat de Barcelona, Spain. Instrument: Coulter LS 13320 equipped with a Universal Liquide Module (ULM). Solvent: purified water / mineral oil. Results: plotted as a histogram, expressing the relative frequency of the number of particles (%) in front of the particle diameter (0.04 μm– 2000 µm). Determination of z-average particle size and polydispersity index The average particle size as described in this document is determined by dynamic light scattering (DLS), which is based on the physical concept of the Brownian motion of particles, defined in the Stokes-Einstein equation: where: d(H) = hydrodynamic diameter D = translational diffusion coefficient k = Boltzmann’s constant T = absolute temperature η = viscosity Without wishing to be limited to any particular theory, the Stokes-Einstein equation establishes that particles suspended in a liquid medium are in a constant and random movement, with a speed that depends on their size: the larger the particle is, the slower the Brownian motion will be. In dynamic light scattering measurements, the sample containing the particles to be measured is illuminated with a monochromatic light source, preferably a laser, and it is analyzed in a correlation function how the intensity of scattered light fluctuates with time. If, for instance, large particles are being measured, as they move more slowly, the intensity of scattered light fluctuates more slowly, and the correlation takes longer time to decay; on the other hand, if small particles are being measured, as they move more quickly, the intensity of scattered light fluctuates more quickly, and the correlation of signal decays more rapidly. According to this invention, the particles are preferably measured with the following instrument: Zetasizer nano zs (Malvern Instruments), using purified water / mineral oil as solvents. If nothing to the contrary is indicated, the instrument is used according to the manufacturer’s instructions, and adjustment and calibration, if applicable, are also performed according to the manufacturer’s instructions. The size is calculated from the correlation function using various algorithms. In the present case, the “cumulants analysis” as defined in ISO13321 Part 8 is applied. The correlation function fits results in a single exponential curve which allows for calculation of the following parameters: -The mean size, or z-average diameter, of the particle distribution. This meansize is the intensity mean. -The polydispersity index (pdi), i.e. corresponding to the width of the particlesize distribution. The results are typically plotted as a histogram, expressing the relative frequency of the number of particles (%) with respect to the particle diameter which may be any diameter which is comprised in the range from 1 nm to 3 μm. Evaluation of immunological effects Measuring antigen-specific T cell responses at the single cell level can give valuable insights in the study of disease pathogenesis and the evaluation of vaccines. In this study, two complementary approaches were used: (1) AIM assays have proven to be an accessible and rapid means for antigen-specific T celldetection. This assay can easily identify and phenotype a wider breadth of antigen- specific T cell responses compared to other proliferation or cytokine-secretion assays. (2) The ICS assay is a multicolour staining process that can reveal exclusive or mutual co-expression of different cytokines in individual cells. This facilitates the characterization of T cell subsets on the basis of cytokine production rather than just surface markers. Evaluation of efficiency Demographic and cancer-related data were collected in order to characterize the study population: gender, age, body mass index, previous BCG vaccination, cigarette smoking status, ASA, date of cancer diagnosis, cytological results, presence or absence of CIS, tumour stage, grade, size and number of tumours, details, and date of TURBT. Efficacy assessments consisted of collecting data of: (1) Recurrence;(2) Disease worsening: events that included diagnosis of T2 or greater, cystectomy,systemic chemotherapy, radiation therapy or other therapy indicative of abandonment of strategies for treatment of NMIBC; (3) Death date and causes. EXAMPLES The invention is in the following illustrated by examples. The examples are for illustrative purposes and should by no means be understood as limiting the scope of the present invention.Example 1: Isolation of the strain Mycobacterium tuberculosis NCTC 13536The starting material for the production of FCMtb (drug substance) is an inoculum of the strainwith deposit number NCTC 13536, synonymously called 511 or Mycobacterium tuberculosisNCTC 13536 or Mycobacterium tuberculosis strain RUTI, a strain of Mycobacteriumtuberculosis isolated from an immunocompetent patient diagnosed with pulmonary tuberculosis in Barcelona, Spain. It was deposited by Archivel Farma S.L. on December 3, 2010 at the NCTC in London, which is an official depositary organisation according to the Budapest Treaty. The strain has additionally been deposited by the strain collection of the Service of Microbiology of the Hospital de Sant Pau, Barcelona, Spain. Two passages of the original strain have been performed in the years 1995, and 1996respectively. MSL PB#1 corresponds to the second passage of the original strain of M.tuberculosis NCTC 13536, which was performed in October 1996 resulting in 100 vials (3 mL sterile glass vials) stored at -70 ± 5 °C. The strain has a low genetic polymorphism, as identified by standard methods in the art. Example 2: Upstream process for production of the drug substance: production of MTB-C cells A flow chart of this process is given in Figure 1. The starting material for the production ofFCMtb (drug substance) is an inoculum of the strain Mycobacterium tuberculosis NCTC 13536(Example 1). In order to ensure the continued supply of this starting material, a seed lot system is preferably used. Hence, a working seed lot (WSL) derived from a master seed lot (MSL) is used for production of FCMtb. Table 2: current in-process controls (IPCs) performed in the upstream process Step of IPC Parameter Acceptance the Test Objective number controlled criteria process Thin layer of MtbVisual inspection of Visualculture To check growth and absence ofStep 1 IPC1 Mtb culture afterinspection Absence of contamination 9 ± 1 days contamination Incubation period TimeTo check that the incubationIPC2 15–-16 days of Mtb cultureobservation period has been achieved Visual inspection of Ivory colour, To check the correct colour and Visual IPC3 growth after 15–16 roughappearance of Mtb culture andinspection days appearance absence of contamination Maintenance of the 37 °C ± 1 °C 37 °C temperature Temperature temperature conditions during IPC4 from 0 to 15–16 37 ± 1 °C control the whole incubation period to days ensure appropriate growth Final inoculum 0,75E+08 –To control the concentration of viable Viable plate IPC5 3,00E+08Mtb viable of final inoculum afterconcentration count Step 2 CFU / mL seeding on 7H11 plates (CFU / mL) To ensure the absence of bacterial Final inoculum Sterility (Ph. and fungal contamination in the IPC6 Sterile sterility Eur.2.6.1)Mtb inoculum prior to and duringseeding on 7H11 plates Visual inspection of VisualPresence of Mtb To ensure the presence of MtbIPC7 Mtb culture after inspection culture culture <10 days Visual inspection ofTo ensure the presence of MtbMtb culture on Visual culture and absence of IPC8 Ivory colour plates after 14 ± 2 inspection contamination by visual days inspection To ensure that 37 °C temperature 37 °C from 0 to Temperature conditions have been maintained IPC9 37 ± 1 °C 21 ± 1 days control throughout the whole incubation period until harvest Step 3 Confluent Visual inspection of appearance To control appropriate Mtbmycobacterial Visual IPC10 Ivory colour culture and absence of growth on plates inspection Absence of contamination after 21 ± 1 days contamination Step of IPC Parameter Acceptance the Test Objective number controlled criteria process To ensure the absence of bacterial Sterility of the Sterility (Ph. IPC11 Sterile and fungal contamination in the HMtb Eur.2.6.1) HMtb prior to freezing (1) Culture of Mtb WSL The production of the DS begins with the thawing of one vial of WSL batch. Each WSL vial contains 0.5 mL and is used to produce two WSL cultures that are run in parallel. To that purpose, for each WSL culture, 0.2 mL of the WSL are seeded on 7H11 agar plates and incubated at 37 ± 1 °C for 15–16 days. A visual inspection of the growth and absence of contamination is performed after 9 ± 1 days of incubation (IPC1). (2) Harvest of Mtb WSL and expansion of Mtb cultureAfter 15–16 days of incubation of Mtb WSL, completeness of incubation period is recorded(IPC2) and a visual inspection of the growth is carried out to check the appearance and colour of bacterial culture (IPC3). The register of temperature is controlled to confirm that the incubation temperature of 37 ± 1 °C has been maintained throughout the whole incubation period (IPC4).Colonies from the Mtb WSL culture are then transferred into a tube containing a few glassbeads and, water for injection is added up to a final concentration of 9–10 mg / mL of Mtb toobtain the Mtb inoculum for culture expansion. After mixing the bacterial suspension, 200 -1008 7H11 agar plates are seeded with Mtb inoculum using sterile swabs soaked with thebacterial suspension to obtain confluent cultures. The plates are incubated at 37 ± 1 °C for 21 ± 1 days under atmospheric control. At this point, two IPCs are carried out on the final inoculum suspension (the inoculum after plates seeding): a final inoculum viable concentration (CFU / mL) (IPC5), and final inoculum sterility test (IPC6). During incubation of seeded plates at 37 ± 1 °C, a visual inspection of the growth and absence of contamination is performed before 10 days of incubation (IPC7) and after 14 ± 2 days (IPC8). (3) Harvest of Mtb and freezing After 21 ± 1 days of incubation at 37 ± 1 °C and before harvesting, a temperature register is checked to confirm that the incubation temperature of 37 ± 1 °C has been maintained throughout the whole incubation period until harvest (IPC9). Afterwards, bacterial growth iscollected from agar plates and transferred into sterile tubes to obtain the Harvest of Mtb(HMtb). A visual inspection is performed to check appropriate Mtb growth and purity of thebacterial culture while harvesting and the final register is done once harvest has been finished (IPC10). The weight of HMtb should be in the range of 72–400 g. HMtb is then frozen and stored at -80 °C ± 5 °C. Sterility test of the HMtb is carried out on the first plate harvested (IPC11). Example 3: Downstream process for production of the drug substance A flow chart of this process is given in Figure 2. Table 3: current in-process controls (IPCs) performed in the downstream process Step of the Parameter Acceptance IPC number Test Objective process controlled criteria pH of the 4%To ensure theIPC12 TX-100 in PBSpH test strip pH 7.0-7.7reproducibility of the solution process pH control of To control the successful IPC13 fragmentedpH test strip pH 6.4-7.0completion of cell cells (SN-sd) fragmentation Visual Step 4 To ensure the efficiency inspection of the Visual Clear and of centrifugation and IPC14 SN after second inspection Colourless PBS washes at removing high-speed lipid supernatant centrifugation To ensure the absence Sterility of the Sterility (Ph. IPC15 Sterile of bacterial and fungal PBS Eur.2.6.1) contamination Cell viability of <1.0E+09 FCMtb Viable count To ensure cell viability Step 5 IPC16CFU / totals suspension plate before pasteurisation < 80ml (CFU / mL) FCMtbTo ensure the sterility ofSterility (Ph. Step 6 IPC17suspension Sterile the suspension after Eur.2.6.1) sterility pasteurisation (4) Cell fragmentation and delipidation (purification) The frozen HMtb (Example 2) is thawed by means of a thawing slope (STEP 1: 10 h at 10 °C (0.1 °C / min); STEP 2: 6 h at 4 °C (0.1 °C / min) and STEP 3: >18 h at 8 °C (0.1 °C / min). Sterile PBS buffer with 4% triton-X100 (pH 7.0–7.7, see IPC12) is then added and subsequently transferred into a sterile fragmentation tank containing sterile silica-zirconia beads. Then, cell fragmentation is carried out in bead mill equipment at 4500 rpm for 45 min at 20 ± 2 °C. Once the process is finished, the cellular fragmented fraction is separated from the beads by subsequent washings (repeated shaking and sedimentation cycles) in sterile PBS buffer with 4% triton-X100 (pH 7.0–7.7). At this point, a pH control of the cell fragments (supernatant) is carried out (IPC13). Afterwards, a final centrifugation at 845 g at 4 °C for 30–45 minutes is performed to separate cell fragments from whole bacilli and beads. The supernatant is harvested. To remove cytosolic fraction and get a suspension enriched in cellular fragments, the supernatant is centrifuged twice at high speed (27.000 g) approx. for 60 minutes, at 4 °C. After the first centrifugation the yellowish supernatant (rich in soluble proteins and lipids) is discarded, and the pellet is resuspended in PBS and further centrifuged at the same above described conditions. After that, the appearance of the discarded supernatant (IPC14) must be clear and colourless. The obtained pellet is weighed (>10 g) and resuspended with an appropriate volume of sterile PBS (45–150 mL) to obtain a maximum concentration of 0.2 mg / mL (DS or FCMtb suspension). Besides, the sterility of the PBS used for the purification of cell fragments and pellet resuspension is tested (IPC15). (5) Pasteurization In order to inactivate the residual bacilli, the whole bulk of DS, FCMtb (drug substance) suspension, is pasteurised at 65 ± 2 °C for 60–65 min. However, before pasteurisation, an aliquot of FCMtb suspension is taken out for testing cell viability (CFU / mL) (IPC16). Once material is subjected to pasteurisation, it will be physically segregated from untreated material, i.e., spaces used up to pasteurisation are clearly separated from those used during the subsequent filling process. (6) Filtration and filling After pasteurisation, the bulk of DS is transferred from the BSL3 room to a positive sterile room (B / A-1 class). Elimination of residual beads is performed through filtration (40 µm), and sterile and depyrogenated vials are filled with 0.5–2 mL of the FCMtb suspension. Four filled vials are used for sterility testing (IPC17). Finally, filled vials are freeze-dried.(7) Freeze-drying, encapsulation, and labellingAll vials are lyophilised at about -45 °C to 30 °C temperature and at 0.310 mbar pressure for approximately 18 hours (0.5 mL volume per vial) and under N2atmosphere. Once lyophilised, vials are encapsulated and labelled and capped using aseptic techniques. This is a continuous process: filled vials are visually inspected and if they are satisfactory (judged based on appearance of the cake, correct dose, non-broken vials), they are first capped with an aluminium cap and subsequently labelled (if visual inspection of capped vial is correct) as follows: ^number of vial,^ name of the product,^ batch code,^ manufacturing date,^ storage condition,^ shelf-life.Overall, vials are visually inspected after freeze-drying, during capping and during labelling. The packaged DS is then stored at -20 °C ± 5 °C. Example 4: Protein characterisation of the drug substanceBased on literature (Andersen P., 1997, Sc and J. Immunol.; 45(2):115-31; Geisel et al., 2005,J. Immunol.; 174(8):5007-15; Stewart et al. 2005, Infect. Immun., 73(10):6831-7., Wang et al.,2007, J. Mol. Biol., 366(2):375-81 Rodriguez-Hernandez, et al. 2020, Biomed and Biotechnol21(11):856-870; Meier et al., 2018, Frontiers in Immunology Vol 9 Article 2476), some protein bands were selected as being representative for protein profile assessment: Heat shock protein (HSP) 70 protein (Rv0350); Phosphate binding (PsTS1) (38 kDa) protein (Rv 0934); outer cell wall antigen 85 complex (30–34 kDa) (Rv3804c & Rv1866c); Heat shock HSP16 (16 kDa) protein (Rv 2031c); 19 kDa protein (Rv 3763), CFP10 protein (Rv3874), and ESAT-6 protein (Rv3875). (A) Determination of total protein content: Total protein levels in FCMtb are quantified by bicinchoninic acid (BCA) methodology. Total protein represents about 15% (w / w) of FCMtb content. Reference standards FCMtb-81, FCMtb-83, FCMtb-86 and FCMtb-87 contain 189, 187, 150 and 160 μg protein / mg FCMtb, respectively. (B) Identification of protein profile by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE): The protein profile of the drug substance FCMtb was determinedby comparison with reference antigens from Mycobacterium tuberculosis corresponding toESAT6 (6 kDa) (7); CFP10 (10 kDa) (6); HSP16 (16 kDa), Ag85 complex (30–34 kDa) (1); PsTS1 (38 kDa) (2); HSP70 (70 kDa) (4); as well as Molecular Weight marker MW (5) (Figure 3). Determination of the protein profile of drug substance FCMtb and identification of bands (approximately 70 kDa, 38 kDa, 30–34 kDa and 16 kDa carried out by Coomassie staining (Figure 3a). Identification of the 19 kDa (lipopolypeptide), 10 kDa, and 6 kDa band is carried out by silver staining (Figure 3b). (C) Identification of the protein profile by Western-blot with specific monoclonal antibodies: The protein profile of the drug substance FCMtb is determined by the patterns obtained using Western-blot analyses with monoclonal antibodies (mAb): Anti-HSP70 (70 kDa), anti-PsTS1 (38 kDa), anti-Ag85B (85 complex 30–34 kDa) and Anti-HSP16.3 (16 kDa) (Figure 3c). FCMtb-81 is the reference batch for FCMtb (drug substance) according to the preferred mode of carrying out this invention. Example 5: Lipid characterisation of the drug substance The characterisation of the lipid profile of FCMtb (drug substance) consists of a fractionating process based on chloroform:methanol (1:1) extraction. The fractionating process carried outin these studies has been based on the procedure described by Delmas et al., 1997,Glycobiology 7(6), 811-7. Thin layer chromatography (TLC) has been the method used to analyse the content of lipids and glycolipids present in FCMtb. Specifically, polyacyltrehalose (PT), trehalose dimycolate (TDM), diacyltrehalose (DAT), sulfolipids (SF) and other phospholipids, as well as Mycolic acids have been identified by thin layer chromatography (TLC) both in different FCMtb batches. The content of trehalose 6,6’-dimycolate (TDM) is analysed by TLC in the supernatant (Figure 4a). Mycolic acids determination is conducted in the sediment, following a TLC method (Figure 4b). Although no quantitative data are known for the lipid profile of MTB-C, the qualitative lipid profile established in the studies is in line with current scientific knowledge and allows for a standard characterisation of the immunogenic lipids currently known. Overall, the lipid content was consistent in different batches of FCMtb-comprising liposomes according to this invention. Figure 4c shows the identification of LAM and LM. Example 6: Characterisation of fragmented cell material Preliminary results show that the fragment size of FCMtb (drug substance) is mainly below 1 μm (99% < 1 μm) which is corroborated by FCMtb electronic microscopy: the fragment size ranges mainly from 100 to 300 nm. Levels of residual DNA after extraction with a phenol / chloroform mixture have been investigated by absorbance at 260 nm (detection limit: 0.2 μg DNA / mg FCMtb). Typical results obtained so far are below 10 µg DNA / mg FCMtb. The consistency of the production process of the drug substance is shown by a lipid and protein profile that is reproducible for different FCMtb batches. Example 7: Effect of sucrose In an initial test, one of the following excipients (a) 1.5% glycine and (b) 5% sucrose, respectively, was optionally incorporated into a liposome formulation comprising fragments of the MTB-C strain NCTC 13536. Subsequently, a comparative evaluation is undertaken on physicochemical properties and biological activity associated to both formulations. Results obtained by measurement after reconstitution of the lyophilized liposome composition and after testing according to the current batch release specification parameters are presented in Table 4. Table 4: Results of RUTI® substance release specification for 3 different formulations, measured after reconstitution of the lyophilized liposome composition FCMtb formulated in a liposome suspension Without Sucrose Glycine Parameter Acceptance criteriaexcipient 5% 1.5% FCMtb formulated in a liposomal suspension Appearance White to off-white powder ND Complies CompliesCake morphology Flat to almost flat andND Complies Complieshomogeneous Water content (%) ≤3 % ND 1.4 3.0Time to reconstitution (s) Well reconstituted ≤10s ND 5 12pH 7–8 8.1 7.4 7.0Particle size 370(1)66 504(1)75 ± 20 (≤0.250) z-average (nm) Pdi (a) (0.492) (0.215) (0.569) Immunogenic potency in 3-12 Ratio SFU / 106 M. Tuberculosis cells with respect infected murine model PPD to basal value 3.6 (183) 5.1 (183) 2.8 (183) Antigen-specific IFN-γ (Basal value in Spot forming units SFU / 106 cells) 5–20 Ratio SFU / 106 cells with Ag85B 5.4 (73) respect to basal 5.5 (73) 9.6 (73) value (Basal value in SFU / 106 cells) (a) Polydispersity index (1) Presence of liposomal aggregates ND = not determined The investigators of this study surprisingly found that 5% sucrose formulation provides the advantage of better physicochemical results, such as water content or time to reconstitution, respectively. But the most crucial fact is the important reduction in liposomal aggregation (particle size, z-average) shown with the sucrose-comprising formulation in comparison with the other two formulations. Analysis by Dynamic Light Scattering has shown a z-average of 75 ± 20 nm (polydispersity index ≤0.350) of the sucrose-containing liposomes. Electron microscopy of freeze-fracturing preparations of the sucrose-containing liposome formulation shows a mixture of multilamellar and unilamellar liposomes with sizes between 40 and 100 nm (Figure 5). Due to this improved parameter together with the observed lesser water content levels (≤2%) for the 5% sucrose formulation, improved stability results are expected for this formulation. This is indeed the case. Example 8: Manufacturing process of lyophilised liposome formulation (drug product) One embodiment of the manufacturing process of a pharmaceutical composition comprising the liposome formulation according to the present invention is shown in Figure 6. The manufacturing process of the drug product, most preferably RUTI®, can be divided into the following main steps: -Step 1: Preparation of the LCS bulk components- Step 2: Preparation of LCS bulk- Step 3: Dilution of LCS bulk to obtain the LS bulk and final sterilization by filtration- Step 4: Filling- Step 5: Lyophilisation, encapsulation, labelling and packaging(1) Preparation of the LCS bulk components The lipid phase of the liposomes consists of soy lecithin solution, sodium cholate solution, and the DS (FCMtb, see Examples 1-6). Soy lecithin is dissolved in Ethanol absolute GR (1:1; w / w) and sodium cholate is dissolved in WFI (1:5; w / w). The solutions are sterilized by filtration through 0.2 µm membrane filters. The lipid phase is prepared in a class C room. The aqueous phase consists of 0.9% sterile saline solution (NaCl) diluted with sterile WFI to obtain a 0.34% final saline solution. This saline solution is prepared in a clean Class A / B room. (2) LCS bulk preparation For the preparation of the LCS bulk a mix of sodium lecithin solution and sodium cholate solution is needed; afterwards lyophilised FCMtb is added upon stirring. The ratios of the components are 0.03:0.2:0.7 (FCMtb (drug substance):sodium cholate:soy lecithin; w / w / w). The aqueous phase is transferred to a sterilised stainless-steel mixer. The lipid phase (containing soy lecithin, sodium cholate, and DS FCMtb) is then added in a ratio 2.7:1 (aqueous phase:lipid phase, w / w). The phases are mixed at 22000 rpm for 3 minutes for homogenisation and liposome formation. After homogenisation, the bulk LCS is transferred to another vessel and allowed to stand for at least 5 minutes. An in-process Control on particle size is performed on the LCS bulk. (3) Dilution of LCS bulk to obtain the LS bulk and sterilization by filtration A 6.0% (w / w) solution of sucrose is prepared with WFI and sterilized by filtration (0.2 µm membrane filter). The sucrose solution is then mixed with sterile WFI and LCS bulk in the adequate proportions to obtain the final LS bulk constituted of 10.5 mg LCS / mL in 5% sucrose solution (1.2 L), which is sterilized by filtration (0.2 µm membrane filter). Before use of the filter and after filtration, controls for filter integrity are performed. PCs are carried out before and after sterilized filtration: visual inspection (IPC2), contamination test (IPC 3), particle size (IPC4) and sterility (IPC5). (4) Filling Vials are filled with 0.4 mL of LS bulk (under continuous agitation) and partially closed for lyophilisation. (5) Lyophilisation, packaging, and labelling The lyophilisation process is performed in the range of -45 °C to 25 °C temperature and 0.150 mbar. The process lasts for 27 hours. After lyophilisation, vials are fully stoppered under a N2atmosphere. Then the vials are encapsulated, labelled, and stored at 5 °C ± 3°C. Visual inspections of each vial are performed throughout this process, after lyophilisation, after encapsulation and after labelling. The label contains the following information: -Number of vial- Name of the product- Batch code- Manufacturing date- Storage condition- Shelf life- “Experimental use”For the clinical batch, the label contains the requirements stated in GMPs. Example 9: Design of clinical phase I trial and patient selection The liposome formulation RUTI® (drug product, Examples 7–8) comprising detoxified,pasteurized, and liposomal cellular wall fragments derived from Mycobacterium tuberculosis-complex FCMtb (drug substance, Examples 1–6) used in this example is the most preferred embodiment of the present invention. It is referred to correspondingly in the following examples, including all associated figures. The dosage refers to the dosage of the drug substance, FCMtb. Objective The objective was to perform a clinical phase I study with the aim of evaluating the efficacy of RUTI® as prime therapeutic cancer vaccination as well as immunological changes associated with RUTI® vaccination. Experimental design Patients diagnosed with high-risk NMIBC, treated with transurethral resection of bladder tumor (TURBT), suitable for BCG therapy and who met all eligibility criteria (see below) were enrolled. The study was conducted on 40 adult patients (aged ≥ 18 years), who had primary histologically confirmed T1 and / or high-grade tumours and / or CIS, and where all visible papillary tumours had been completely resected. Patients were furthermore selected to have no disease that could compromise the assessment of the response to the vaccination or would increase the risk of adverse events. Only patients who had never been treated with BCG immunotherapy previous to the present study were enrolled. Patients with active tuberculosis at screening visit and patients who had received TURBT within 14 days of the start of treatment were not included. Patients were assigned into a study group, which received RUTI® vaccination, and a placebo control group. Both groups received BCG treatments as outlined below. Assignment into these groups was performed in a randomised manner in a 1:1 ratio. The study design and timepoints of administration of RUTI® and BCG are shown in Figure 7. INCLUSION CRITERIA 1. Written ICF for participation in the study. 2. Age ≥18 years. 3. General health status according to WHO ≤ 2. 4. Have primary histological confirmed T1 and / or high-grade tumors and / or CIS. 5. All visible papillary tumors must be completely resected. 6. Early postoperative (within 24 hours of TURBT) single dose chemotherapy was allowed. 7. BCG therapy indication. 8. Never treated with BCG immunotherapy 9. Willing to comply with study visits and procedures as per protocol 10. Use of reliable contraception (see section 8.6) from the screening visit to 30 days after the last RUTI® or placebo injection EXCLUSION CRITERIA 1. Life expectancy <5 years. 2. Have a severe concomitant disease that might limit compliance or completion of the protocol. 3. Have any other malignancy that might impact 3-year survival or might be potentially confused with NMIBC. 4. Have other neoplasms. 5. Have congenital or acquired immune deficiencies or under immunomodulatory treatment. 6. Be receiving cytotoxic drugs or systemic corticosteroids within 8 weeks of receiving the first administration of BCG. 7. Have received radiation therapy for their bladder cancer within 4 months prior to study entry. 8. Have active infections (including urinary tract infections) defined as viral, bacterial, or fungal infections requiring therapy, HIV-positive status, concurrent febrile illness, gross hematuria or other factor that could influence tolerability to intravesical BCG therapy. 9. Have biopsy, TURBT, or traumatic catheterization within 14 days of start of treatment. 10. Have active tuberculosis at screening visit. 11. Active pregnancy or breastfeeding. 12. Soy allergy. Treatment with RUTI® or placebo Patients assigned to the study group received RUTI®, as defined below, in a dose of 25 μg FCMtb (corresponding to 0.3 mL injection volume) twice. The second dose was applied ten days after the first dose. Herein, “RUTI1” (day 0) denotes the day the first dose of RUTI® was administered, and “RUTI2” (day 10) denotes the day the second dose was administered. The treatment was administered via subcutaneous injection into the deltoid region of the arm. Quantitative and qualitative composition of RUTI® vaccine per vial Component Amount per vial FunctionDrug substance FCMtb 33.3 µg ImmunogenExcipients Sucrose 20,000.0 µgCharge substance (freeze-drying) and cryoprotector Soy lecithin1 422.9 µg Liposome forming agentSodium cholate 46.0 µg TensoactiveSodium chloride2 10.4 µg Isotonic agentEthanol3 q.s. SolventWater for injection q.s Solvent1Containing Phosphatidylcholine (NLT 94.0%) 2 Added as NaCl 0.9% solution 3It disappears in the course of processing Patients assigned to the placebo group received 0.3 mL sterile saline solution (0.9% NaCl [w / v]) on day 0 (RUTI1) and day 10 (RUTI2) via subcutaneous injection into the deltoid region of the arm. Intravesical BCG treatment Following RUTI® / placebo administration, all patients from both groups received intravesical BCG therapy, as defined herein, which consisted of (1) an induction course and (2) a maintenance course: (1) during the induction course, patients received weekly BCG over six weeks. Thefirst dose was administered six days after RUTI2. The days on which BCG treatment was administered are denoted as BCG1–BCG6, with BCG1 denoting the first day and BCG6 the sixth day. Four to eight weeks after the last intravesical BCG administration (BCG6), a visit was performed (VISIT 1) which marked the end of the interventional phase. Once all patients had completed VISIT 1, immunological assays were performed, and data was analysed (Example 10).(2) during the maintenance course, patients received 3 courses of weekly BCG overthree weeks at 3, 6 and 12 months after induction. The BCG therapy was administrated according to the internal practices of each hospital and encompasses BCG products commercialized for the administration to patients diagnosed with high-risk NMIBC. See the above section “Definitions” for further details. Regarding the BCG regimen administered, most of the patients in both groups received maintenance therapy: 17 patients (85%) in RUTI® group and 15 patients (75%) in the placebo group. All patients were followed up upon with clinical visits for three years after TURBT (“follow-up phase”). The study was performed in a double-blind set-up: Clinical investigators, study nurses, and patients were blinded to the treatment allocation. Only pharmacy staff preparing the syringes for administration were not blinded to treatment allocation. Masking was not needed because the appearance of placebo did not differ from that of RUTI®. At the end of the “interventional phase”, the blind was opened, except for the study physicians, who remained blind during the follow-up phase. Results Analysed datasets All patients who were randomized were analyzed. A total of 44 patients with high-risk NMIBC was enrolled in the study. Four patients declined to participate before randomization due to personal reasons. Forty patients were randomized to receive two doses of either placebo (n=20) or RUTI® (n=20). The immune response was analyzed in 18 placebo and 20 RUTI® patients. The analysis was not performed in 2 placebo patients as the number of PBMCs collected was not sufficient for the analysis. Thirteen and sixteen patients completed the three-year follow-up in the placebo and RUTI® groups, respectively (Figure 8). Baseline characteristics of the patients All patient characteristics at baseline were similar in both treatment groups (Table 5). Although weight was slightly higher at baseline in RUTI® vaccinated patients and placebo patients were slightly more likely to smoke, differences were not statistically significant. There were no significant differences in age, gender, or BMI between groups. The blood biomarkers associated with systemic inflammation neutrophil-lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) were analyzed before vaccination and no differences were observed among groups. However, despite the study being conducted through a double-blind randomization process, an imbalance in tumor characteristics between the groups was observed. This discrepancy may be attributed to the relatively small sample size, which increases the likelihood of chance-driven differences between study arms. Tumor classification was 67.5% high-grade T1 and 32.5% Ta, with 4% having concomitant CIS (all in the placebo group). Multiple lesions were more frequent in the placebo group compared to the RUTI group (60% and 25%, respectively; p=0.049). Small tumors (≤ 3 cm) were evenly distributed. To compensate for this imbalance in the efficacy evaluation, an exploratory analysis was conducted including only high-grade T1 patients without CIS, while also balancing other tumor characteristics (Table 6). The immune composition of circulating T cells (CD4+ and CD8+) and the expression of the CD27 memory protein at baseline (i.e. before treatment with the liposome formulation of the present invention or with placebo) was analysed by flow cytometry in cryopreserved PBMCs collected at baseline. We observed a higher, although not significant proportion of CD4+ T cells in the placebo group when compared to the RUTI® group (p=0.07; Figure 9). A slightly higher proportion of CD8+ T cells was observed in RUTI® patients, with a significant increase in the CD8+CD27- T cell subset (p=0.04). Statistical analysis Patient demographics analysis was performed using a Fisher exact test to compare categorical variables and a Mann-Withney U nonparametric test to compare continuous variables between vaccinated groups. Table 5. Patient demographics and immune composition at baseline Total populationVaccine Administered PLR, median (IQR) 105.5 (68.58- 103.4 (79.10- LMR, median (IQR) 2.9 (1.6-4.1) 3.4 (2.3-4.6) 2.5 (1.2-3.5) 0.115IQR = Interquartile range; L = liter; NLR = neutrophil-lymphocyte ratio; PLR = platelet-lymphocyte ratio; LMR = lymphocyte-monocyte ratio. *Comparison of RUTI® and Placebo groups (Mann-Withney U or Fisher exact test).

[0003] Table 6. Efficacy Analysis. All population and High-grade T1 cohort All population High-grade T1 cohortRUTI Placebo p-value*RUTI Placebo )p-val* (N = 19) (N = 18) (N = 10(N = 11) ueAge (years), median (IQR) 71 (62-75) 67 (61-74) 0.6 73 (69-78) 68 (64-74) 0.24Gender (male), n (%) 17 (89.5%) 17 (94.4%) >0,9999 8 (80%) 11 (100%) 0.21Cancer stages, grades and CIS T1 HG 10 (52.6%) 11 (61.1%) 10 (100%) 11 (100%)T1 BG 0 (0%) 1 (5.5%) - -Ta HG 9 (47.4%) 2 (11.1%) - -T1HG+CIS 0 (0%) 3 (16.6%) - -TaHG+CIS 0 (0%) 1 (5.5%) - -Nº of lesions, n (%) 0.04 >0.99Solitary 13 (72.2%) 6 (35.3) 5 (50%) 4 (40 %)Multiple 5 (27.8%) 11(64.7%) 5 (50%) 6 (60 %)No documented 1 (5.2%) 1 (5.6%) 0 (0%) 1 (9.1%)Tumor size, n (%) >0,9999 0.66Small (≤1-3 cm) 10 (62.5%) 9 (60%) 3 (37.5%) 5 (50%)Large (>3 cm) 6 (37.5%) 6 (40%) 5 (62.5%) 5 (50%)No documented 3 (15.8%) 3 (16.6%) 2 (20 %) 1 (9.1%)IQR= Interquartile range; *Comparison of the RUTI and placebo groups (Mann‒Whitney U test or Fisher’s exact test).

[0004] Example 10: Immunological effects of RUTI® vaccination as determined by evaluating the systemic Th1 immune response The liposome formulation RUTI® (drug product, Examples 7-8) comprising detoxified,pasteurized, and liposomal cellular wall fragments derived from Mycobacterium tuberculosis-complex FCMtb (drug substance, Examples 1-6) used in this example is the most preferred embodiment. It is referred to correspondingly in the present example, including all associated figures. The dosage refers to the dosage of the drug substance, FCMtb. Objective The aim of the experiments outlined in the following was to evaluate the immunological changes induced by RUTI® in human subjects in the clinical study of Example 9. Immunological effects of RUTI® were analysed by evaluating the systemic Th1 immune response at different timepoints throughout the interventional phase. Experimental design Immunological changes were evaluated at timepoints RUTI1, BCG1, BCG6,and VISIT1 in patients from the clinical study of Example 9. Table 7 summarises clinical assessments, treatments, and samples taken from patients for analysis at different timepoints of the clinical study. Table 7: Study Flow Chart Interventional Phase Follow-upStudy Up to 3 Visit ProcedureTURBT SCR RUTI1 RUTI2 BCG1 BCG2-5 BCG6years from 1 TURBT Day-1 BL Day 10 W16Visit window Informed X Consent Clinical Visit X X X X RUTI® / Placeb o XXAdministratio n Blood X X X X XUrine X X X X XIntravesical XX XBCG Tissue (Biopsy) X X*Cystoscopy X*Ultrasound scan Cytology XPicture of XX Xinjection site Adverse Event XTURBT: Transurethral resection of bladder tumour; SCR: Screening Visit; BCG: Intravesical BCG therapy; W: Weeks X indicates the assessments performed. Evaluation of immune response For the evaluation of the immune response, timepoints are herein referred to as: BL (RUTI1), W2 (BCG1), W6 (BCG6), and W16 (VISIT 1). The evolution of circulating CD4+ and CD8+ T cells and the two different memory populations defined by the expression of CD27 was analyzed over time in the samples taken at the following time points: before vaccination (BL), 10 days after the second dose of the vaccine (W2), before the last intravesical BCG instillation of the induction course (W6), and 4–8 weeks after the last intravesical BCG administration of the induction course (W16). The specific and the polyclonal immune responses induced over time were also analyzed by stimulating PBMCs with one of four different mycobacterial antigens (PPD, heat-killed BCG, a peptide pool of theESAT-6 protein of M. tuberculosis and the recombinant 16 kDa protein [HSP16.3] of M.tuberculosis), PMA / ionomycin, or the superantigen Staphylococcal enterotoxin B (SEB). Detailed experimental Mtb cell wall fragment containing drug product: The Drug Substance (DS) consists of purified cell wall fragments of Mtb named FCMtb. The manufacturing process of FCMtb comprises cellular fragmentation of harvested bacterial cultures of Mtb (see previous examples). The thus obtained cell wall fragments are purified in presence of Triton X100 to remove soluble components and endotoxin-like molecules. The structure of the DS is closely related to that of the cell wall of Mtb. Thus, DS is composed mainly of a heterogeneous spectrum of proteins and lipids from the Mtb strain. RUTI®, the IMP (drug product), is a DS liposome suspension containing a charge excipient. It is presented as a dry powder for reconstitution with water for injection and it is stable at 5 °C for at least 12 months. Table 8 shows the composition of RUTI®. Table 8: Quantitative and qualitative composition of RUTI® vaccine per vial ComponentDrug FCMtb 33.3 µg Immunogen Charge substance (freeze-drying) and Sucrose 20,000.0 µgcryoprotector Soy lecithin 1 422.9 µg Liposome forming agentSodium cholate 46.0 µg TensoactiveSodium chloride 2 10.4 µg Isotonic agentEthanol 3 q.s. SolventWater for injection 3 q.s. Solvent1 Containing Phosphatidylcholine (NLT 94.0%) 2 Added as NaCl 0.9% solution 3 Removed in the course of processing The RUTI® vaccine was stored in a safe refrigerator at 2–8°C. RUTI® was reconstituted for injection in 0.4 mL water to obtain 83.3 μg / mL FCMtb. Two doses of RUTI®, each containing 25 µg FCMtb (0.3 mL reconstituted RUTI®), were administered to patients assigned to the study group in a ten-day interval. The day the first dose was administered (Day 0) is referred to as “RUTI1” and the day the second dose was administered (Day 10) is referred to as “RUTI2”. The administration was performed subcutaneously into the deltoid region of the arm. Patients assigned to the placebo group received 0.3 mL sterile saline solution containing 0.9% NaCl (w / v) (Meinsol). Administration was performed subcutaneously into the deltoid region of the arm at the same interval as the study group, i.e. on Day 0 (RUTI1) and Day 10 (RUTI2). Following treatment with RUTI® or the placebo, both groups received intravesical BCG therapy following the standard procedure. Assessment of immune response Peripheral blood was obtained at RUTI1 (BL), BCG1 (W2), BCG6 (W6), and VISIT 1 (W16), and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved in liquid nitrogen until further use. Immune response was assessed by multicolor flow cytometryanalysis using two different approaches: Activation-induced marker (AIM) analysis or ex vivoexpression of IFN-γ, IL-2, and TNF-α using intracellular cytokine staining (ICS) as described below. Activation-induced marker (AIM) analysis Ex vivo T cell responses were measured based on T cell activation and surface expression of different receptors. This assay detects cells that are activated as a result of antigen-specific stimulation by upregulation of activation-induced surface markers. Here, we assessedexpression of CD25, CD69, CD137, and OX40, see, e.g., Poloni, C. et al., “T-cell activation–induced marker assays in health and disease”, Immunol Cell Biol, 2023, 101: 491-503. Intracellular cytokine staining (ICS) This method of analysis provides information on the types of cytokines that are expressed upon (antigen-specific) stimulation of T cells, e.g., TNF-α, IFN-γ, and IL-2. See, e.g., Smith SG. et al., “TBVI TB biomarker working group. intracellular cytokine staining and flow cytometry: considerations for application in clinical trials of novel tuberculosis vaccines", PLoS One, 2015;10(9):e0138042. Statistical analysis For the immunological response analysis differences were calculated using a Wilcoxon’s matched-pair signed rank test between paired samples (samples from the same patient), a Mann-Whitney U nonparametric test for unpaired samples (differences between samples in placebo and RUTI® groups), and for fold change analysis a Wilcoxon signed rank nonparametric test (differences compared to 1) *p < 0.05; **p < 0.01, ***p < 0.001. Results Determination of frequency of different immune cell populations To determine the effect of RUTI® alone (vaccine immunogenicity), the frequency of different immune cell populations present in the peripheral blood at W2 was compared to that of BL. In unstimulated conditions and after 10 days of vaccination, no changes were observed in the placebo group in any of the immune cell populations analysed (Figure 10 and Figure 11). RUTI® vaccination resulted in a significant decrease in the frequency of CD8+ T cells (p=0.03) and an increase in CD4+CD27+ T cells (p=0.04) (Figure 10 and Figure 11).Detection of vaccine-specific T cells using activation-induced markers (AIMs) after antigen exvivo stimulation The expression of activation-induced markers (CD25, CD69, CD137, and OX40) on CD4+ and CD8+ T cells was assessed by flow cytometry. Vaccine-specific T cell responses after PPD stimulation could clearly be detected in both CD4+ and CD8+ T cells. A significant increase in all the activation markers relative to BL, calculated as fold change, was observed in the RUTI® group whereas no statistical differences were detected in the placebo group relative to BL (Figure 12). The increase in the response was significantly different between both groups in CD69+ cells, CD4+ T cells, in CD137+, and OX40+ cells and in both CD4+ and CD8+ T cells (Figure 12 A and D). In CD4+ T cells the activation was preferentially observed in the CD27- subset, while in CD8+ T cells there was an upregulation in both CD27 subpopulations, with a higher increase in CD137 and CD25 in the CD27+ subset as well as OX40 in the CD27- subset (CD4+ T cells: Figure 12 B and C; CD8+ T cells: E and F). In addition, the profile of the activated cells was determined by assessing the co-induction of these activation markers. The analysis of dual combinations of these markers showed that RUTI® vaccination induce a significant upregulation of cells that co-expressed different AIMs, being significantly higher in the RUTI® versus the placebo group (data not shown).AIM changes attributable to the RUTI® vaccine were not observed after ex vivo BCG orpolyclonal stimulation with SEB or PMA+ionomycin, neither in CD4+ (Figure 13) nor in CD8+ T cells (data not shown). Detection of vaccine-specific T cells using intracellular cytokine staining (ICS) Frequencies of functional CD4+ and CD8+ T cells producing IFN-γ, IL2, and TNF-α induced after the same stimulations as used in the AIM assay (see above) were monitored using flow cytometry. In contrast to the AIM assay, no significant differences were found between BL and W2 in any of the conditions tested (Figure 14). Effect of RUTI® vaccine on the response to BCG intravesical treatment To evaluate the effect of RUTI® vaccination on the immune response induced by intravesical BCG treatment, we evaluated the immunological changes at W6 and W16 compared to BL. The intravesical BCG-induced immunity was evaluated in the placebo group. After 5 intravesical BCG instillations (at W6), we observed a significant increase in the proportions of CD4+ T cells, mainly CD4+CD27+ T cells, with a significant concomitant decrease in the proportions of CD8+ T cells (Figure 15 A and Figure 10) in this group. Moreover, absolute values were significantly different from those observed for the patients in the RUTI® group (Figure 10). Changes were transitory, with a decrease and an increase in CD4+ and CD8+ T cells, respectively at W16 (Figure 15 A), as well as no differences in the frequencies at W16 from those of the BL (Figure 10). The effect of RUTI® vaccination on the BCG-induced immune response was next evaluated in the RUTI® group. In this group, at W6 there was a slight, although not significant, increase in CD4+ T cells compared to BL. At W16, CD4+ T cells decreased again significantly compared to W6. No differences in fold changes were found in CD8+ T cells (Figure 15 A) compared to BL, although a significant increase in frequencies at W16 was observed compared to the values before vaccination, detected mainly in CD8+CD27- T cells (Figure 10). In the placebo group, intravesical BCG treatment resulted in an increase in activatedCD4+CD25+ T cells in the periphery, which could already be detected without ex vivostimulation (Figure 15 B). CD25+ upregulated cells did not co-express other antigen-specific activation markers such as CD137 or OX40. The increase was transient except for CD25+OX40- cells that remained increased at W16 (Figure 15 B). In the RUTI® group, the increase in circulating CD4+CD25+ T cells was not observed, leading to a significant difference in the increase of this type of cells at W6 between patients in the placebo and RUTI® groups (Figure 15 B). In addition, a significant increase in the percentage of CD4+CD25+CD27+ cells in placebo vs RUTI® group was observed (Figure 15 C). On the contrary, in the RUTI® group, the intravesical BCG treatment was associated with an increase in the periphery of cells expressing CD137, which co-expressed CD25 but not OX40 or CD69, the latter remaining elevated in W16 sample (Figure 15 D). No significant differences were reached between placebo and RUTI® values. In order to further evaluate the antigen-specific response, we analyzed the immune responseinduced following ex vivo PPD stimulation. The placebo group showed a skewed response,with an upregulation of almost exclusively CD4+CD25+ T cells, mainly with a CD27+ phenotype (Figure 16 A). In contrast, in the RUTI® group, we observed that a more balanced and polyfunctional response was induced, with significant increases in CD4+CD25+, CD4+CD137+, CD4+OX40+, and CD4+CD69+ cells (Figure 16 A and B). Moreover, upregulated cells were preferentially CD27- cells in the RUTI® group (Figure 16 B and C). Although the increase was transient, several of the upregulated populations still remained above the BL at W16, namely CD4+CD25+CD27- and CD4+CD69+CD27- in the placebo group and CD4+CD25+CD27-, CD4+CD69+CD27-, and CD4+CD137+CD27- in the RUTI® group (Figure 16). Despite the higher expression of AIMs in the RUTI® group, no significant differences were observed in comparison with the placebo group for any of the analysed AIMs. Nevertheless, a clear difference (p=0.05) was observed at W6 in the CD4+CD69+CD27- population which was strongly upregulated in the RUTI® group. The impact of intravesical BCG therapy on the peripheral CD4+CD25+ upregulation was alsoanalysed after ex vivo BCG and PMA / ionomycin stimulations (Figure 13). No changes wereobserved in CD8+ T cells (data not shown). No increase in any other AIMs was observed after BCG or polyclonal stimulation (Figure 13). The effect of RUTI® vaccination was also analysed by profiling cytokine producing cells after ex vivo PPD stimulation. Changes were evaluated in CD4+ T cells as no changes were detected in any of the CD8+ T cell populations. In addition, and as stated above, no differences were found between BL and W2 samples in any of the cytokines (Figure 14). Therefore, the average of the cytokine production at BL and W2 was calculated and assessed as the “pre-BCG” sample. Significantly higher levels of IFN-γ+, IL2+, and TNF-α+ specific CD4+ T cells were observed in the RUTI® group compared to in the placebo group at W6 (Figure 17 A), with a significant increase in the frequency of total cytokine-expressing CD4+ T cells (Figure 17 B). No significant differences were found between the levels of cytokine-positive cells between groups, but a lower, not significant, increase was observed in the placebo group (Figure 17 A and B). The increase was transient as no differences were observed at W16 in any group. No significant changes in cytokine-producing cells were observed after BCG stimulation between time points and between groups (Figure 14). To evaluate the polyfunctional profile of the induced T cells, a co-expression analysis using Boolean gating was performed. In comparison with placebo patients, a significantly higher increase in antigen-specific polyfunctional CD4+ T cells (bi- and trifunctional) was induced in RUTI® patients at W6 (Figure 17 C). In addition to the described changes in frequencies of antigen-specific induced cells, it was also observed that intravesical BCG treatment was associated with a higher induction of cytokine-producing CD4+ T cells, significant in IL2+ cells, after the polyclonal and non-specific stimulation with SEB (Figure 17 D) and PMA+ionomycin (Figure 14). The increase was observed in both, placebo and RUTI® patients. However, when the polyfunctional capacity of these cells was evaluated, we found that RUTI® group had higher frequencies of trifunctional CD4+ T cells (Figure 17 E). Specific immune response induced by RUTI® vaccine after BCG intravesical treatment To decipher the role of the specific immunity induced by RUTI® in the immune responseinduced by intravesical BCG treatment, two antigens present in M. tuberculosis but not in BCG,such as the peptide pool of the ESAT-6 protein and the recombinant protein HSP16.3, were included in the analysis. We did not observe any significant increase in the specific AIM CD4+ or CD8+ response, only a non-significant increase in CD4+CD25+ T cells in the placebo group which was already observed in non-stimulated samples as described above. On the other hand, when the frequencies of the cytokine-producing cells were evaluated following HSP16.3 stimulation, a different dynamic of the response was observed in the placebo and RUTI® groups: a decrease in the response over time in the placebo group, significant in CD4+ T cells, together with an increase in the RUTI® group, significant in both CD4+ and CD8+ T cells (Figure 18 and Figure 19). The RUTI®-specific response was maintained over time, being significantly higher at W6, in CD4+ and CD8+ T cells, and at W16, in CD8+ T cells (Figure 18). No specific increases in the response were observed with ESAT-6 stimulation (Figure 19). Conclusion of immunological analyses As for vaccine immunogenicity, an increase in specific effector CD4+ and CD8+ T cells co- expressing activation induced markers was observed 6 days after RUTI administration (2nd dose). The increase in RUTI®-specific CD4+ and CD8+ T cells was sustained over time. When used as prime in a prime-boost strategy with BCG as boost, RUTI® vaccination halts the activation and increase (proliferation) of Treg cells induced by BCG. Hence, RUTI® vaccination could be associated with a more balanced, effective, durable, and polyfunctional BCG-specific response compared to the placebo vaccination. Example 11: Efficacy of RUTI® vaccination at 3 years time from treatment initiation The liposome formulation RUTI® (drug product, Examples 7–8) comprising detoxified,pasteurized, and liposomal cellular wall fragments derived from Mycobacterium tuberculosis-complex FCMtb (drug substance, Examples 1–6) used in this example is the most preferred embodiment. It is referred to correspondingly in the following examples, including all associated figures. The dosage refers to the dosage of the drug substance, FCMtb. Objective The aim of the experiments outlined below was to evaluate the efficacy of RUTI® vaccination in human subjects in the clinical study of Example 9. The efficacy was assessed by determining the RFS, PFS, CSS and EFS during the follow-up phase of three years which followed after the interventional phase. Experimental design Patients were treated with RUTI® and BCG as outlined in Examples 9 and 10 and Figure 8. . Follow-up efficacy analyses were performed on data collected from 37 patients, since, as shown in Figure 8, three patients were not followed up. Efficacy assessments consisted of collecting data of (1) recurrence, (2) disease worsening (i.e., events that included diagnosis of T2 or greater, cystectomy, systemic chemotherapy, radiation therapy or other therapy indicative of abandonment of strategies for treatment of NMIBC), and (3) death date and causes. Recurrence (high- and low-grade recurrence) was defined according to the 2024 EAU guidelines. High-grade recurrence is defined as any histology-proven high-grade disease within the bladder occurring during or after BCG therapy (Gontero et al., 2024, Eur Urol.; S0302-2838(24)02514-4). Low-grade recurrence during or after BCG treatment was not considered a BCG therapy failure. Progression was defined as the development of a new tumor with pathologically proven muscle invasion (T2 or greater) and indicative of, cystectomy, systemic chemotherapy, radiation therapy, or other therapy indicative of abandonment of strategies for treating NMIBC. High-grade recurrence-free survival (RFS) and progression-free survival (PFS) were defined as the rate of surviving patients surviving with withoutno evidence of recurrence or progression, respectively. Event-free survival (EFS) rates were calculated, including based on the occurrence of any event indicating BCG treatment failure, namely: high-grade recurrence, disease progression to MIBC, or cancer-related death during follow-up. Follow-up was defined as the time interval between TURB and the event. For patients without recorded death, assessments were performed after follow-up time was defined as the periodperiods of from TURB to 36 or and 60 months from TURBT, respectively for (3- and 5- year assessments, respectively). Patients were censored at the date of death due to other causes or at the date of their last known survival. Cancer-specific free survival (CSS) rates were also calculated based on the occurrence of cancer-specific deaths. Statistical analysis: Probability of RFS, PFS, CSS and EFS estimation Secondary endpoints analysed in this follow-up study included recurrence, progression, and death rates. Probabilities of RFS, PFS, CSS and EFS were estimated and plotted using the Kaplan-Meier method and compared by long-rank test. RFS and PFS were defined as the proportion of patients who survive without experiencing recurrence or progression, where progression is defined as the development of a T2 or greater disease, lymph node or metastatic disease, or receipt of any cystectomy. CSS is defined as the proportion of patients who are alive and have not died from bladder cancer. EFS is defined as the proportion of patients who have not experienced recurrence, propression of die from bladder cancer. Results Efficacy after 3-years from TURBT Table 9-a and Figure 20 show the results of efficacy assessments after 3 years of follow-up. At this point in time, in the entire cohort (n=37), 5 patients (13.5%) experienced recurrence. This included 3 patients in the placebo group and 2 in the RUTI® group, with 4 of these recurrences occurring within the first 6 months of treatment, resulting in recurrence-free survival (RFS) rates of 83.3% and 89.5% in placebo and RUTI® groups (p=0.291). The mean time to recurrence of patients who recurred was shorter in the placebo compared to that of RUTI®-vaccinated patients (4.72 months and 20.32 months, respectively). Progression to muscle-invasive disease (T2 or greater) occurred in 4 patients (10.8%) in the total population, all of which were in the placebo group. This marked a significant difference between the treatment groups, with progression-free survival (PFS) of 77.7% and 100% in the placebo and RUTI® arms, respectively (p=0.032). The total population experienced two cancer-specific deaths (5.4%), both of which were in the placebo group. This resulted in cancer-specific free survival (CSS) rates of 88.9% and 100% for the placebo and RUTI® groups, respectively (p=0.141). Evaluation of the complete response resulted in an event-free survival rate (EFS) of 72.2.% and 89.5% in placebo and RUTI® groups, respectively (p=0.185). As shown in Figure 20, RUTI® administration can be associated with higher RFS, PFS, CSS and EFS. Table 9-a. Patient outcomes at 3 year follow-up Tumour characteristics The tumour characteristics assessed in the study included histology, tumour location, grade, tumour size, and number of tumours (Table 9-b). Patients were classified as high-grade T1 and Ta (65% and 32.5%, respectively), including 4% with concomitant CIS in the total cohort. Before resection, half of the patients had large tumours (≥3 cm) distributed throughout the bladder. Statistical differences between the two groups were not seen in tumour characteristics or systemic inflammation after intravesical BCG treatment. Statistical analysis Tumour characteristics analysis was performed using a Fisher exact test to compare categorical variables and a Mann-Withney U nonparametric test to compare continuous variables between vaccinated groups.

[0005] Table 9-b. Tumour characteristics

[0006] IQR= Interquartile range; L= liter; NLR= neutrophil-lymphocyte ratio; PLR= platelet-lymphocyte ratio; LMR= lymphocyte-monocyte ratio. *Comparison of RUTI® and Placebo groups (Mann-Withney U or Fisher exact test). Conclusion of efficacy analyses at 3 year follow-up The administration of RUTI® was associated with longer disease-free survival and a with lower number of recurrence and progression events compared to the placebo group, see, e.g., Table 9-a. Example 12: Safety assessment Safety assessments consisted of collecting all adverse events (AEs) and serious adverse events (SAEs) during the Interventional Phase, with their severity and relationship to study drug. To evaluate the injection site the redness, pain, swelling, induration, and functional limitation patients were monitored in visits RUTI2, BCG1and BCG6. The following gradation scale was used: -Mild: Event causing zero or minimal interference in functional activities- Moderate: Event causing more than minimal interference in functional activities- Intense: Event causing inability to perform functional activitiesSafety of RUTI® was determined by analysis of local and systemic reactogenicity. Data were expressed as: -Proportion of patients who developed a Grade 3 or 4 local reactions- Proportion of patients who developed a Grade 3 or 4 systemic reactions- A descriptive summary of any local and systemic events, including severity, durability,and relationship to study product Results RUTI® vaccine was safe and well tolerated. A summary of adverse events (AE) is shown in Table 10. Collectively, 10 patients (25%) across both groups experienced mild AEs (classified as grade 1 and 2). None of the patients experienced more than 2 AEs or serious AEs (SAE). The AEs included injection site reactions; with injection site induration in one patient in each group, and erythema, swelling, and pruritus in 3 patients in the RUTI® group. Other AEs included fatigue, malaise, diarrhea, and pain. Overall, patients in the RUTI® group did not report more AEs than those in the placebo group. All AEs were self-limiting and resolved in the absence of any intervention. RUTI® vaccination before intravesical BCG treatment in patients with high-risk NMIBC is safe and well tolerated and significantly modulates the immune response The immune modulation could be associated with the longer disease-free survival observed in the RUTI®-vaccinated patients.

[0007] Table 10. Systemic and local adverse events (AE) Patients, n(%)Total populationRUTI®Placebo (n=40) (n = 20) (n = 20) Patientsreporting AEs, n (%) 10 (25) 2 (5) 8 (20)Grade 1Typeof AEInjectionInjectionInjectionInjectionInfluenzaFatigueMalaiseDiarrheaVomitingPainArthralgiaAstheniaHematuriaThoracicHypogastricAnemiaEdema Grade 2Thoracic

[0008] Example 13: Efficacy of RUTI® vaccination at 5 years’ time from treatment initiation Objective Efficacy of the RUTI® vaccination was further investigated in a follow-up study over a total period of 5 years from TURBT. The study was approved by the Ethics Committee (PI-24-163). Experimental design The treatment and patients are described in Example 9 and Figure 8. Follow-up efficacy analyses were performed on data collected from 37 patients, since, as shown in Figure 8, three patients were not followed up. Secondary endpoints analysed in this follow-up study included recurrence, progression, and death rates. Recurrence (high- and low-grade recurrence) was defined according to the 2024 EAU guidelines. High-grade recurrence is defined as any histology-proven high-grade diseasewithin the bladder occurring during or after BCG therapy (Gontero et al., 2024, Eur Urol.;S0302-2838(24)02514-4). Low-grade recurrence during or after BCG treatment was not considered a BCG therapy failure. Progression was defined as the development of a new tumor with pathologically proven muscle invasion (T2 or greater) and indicative of cystectomy, systemic chemotherapy, radiation therapy, or other therapy indicative of abandonment of strategies for treating NMIBC. High-grade recurrence-free survival (RFS) and progression-free survival (PFS) were defined as the rate of patients surviving without recurrence or progression, respectively. Event-free survival (EFS) rates were calculated based on the occurrence of any event indicating treatment failure, namely high-grade recurrence, disease progression to MIBC, or cancer- related death. For patients without recorded death, assessments were performed after follow-up periods of 36 and 60 months from TURBT, respectively (3- and 5-year assessments, respectively). Patients were censored at the date of death due to other causes or at the date of their last known survival. Cancer-specific free survival (CSS) rates were also calculated based on the occurrence of cancer-specific deaths. Results after 5 years from TURBT The efficacy of RUTI was evaluated at 5 years. A swimmer plot summarizing the clinical course and treatment response is shown in Figure 21. Due to an imbalance in risk factors (T stage, CIS, and multifocal tumors), favouring the RUTI group (Table 6. All population), a subgroup analysis was conducted, focusing on high-grade T1 patients without CIS (Table 6. High-grade T1 cohort and highlighted in Figure 21). Table 11 and Figures 22 (for the total population) and 23 (for the subgroup as described above, in Figure 21 and in Table 6) show the results of efficacy assessments after 5 years from TURBT. In the 2 years following the first assessment (see above), no further events occurred in the RUTI® arm, while further disease worsening was observed in the placebo arm. Over the total 5-year follow-up period, 5 patients recurred in the placebo group compared to 2 in the RUTI® group (RFS 72.2% and 89.5%, respectively; p=0.193), see Figure 21. When recurrence and RFS rates were calculated including all recurrences (both low- and high-grade) and any progression events occurring as the first event, in the total population (n=37), recurrence occurred in 12 patients: 8 / 18 (44.4%) in the placebo group and 4 / 19 (21.1%) in the RUTI group, with 4 recurrences within the first 6 months (Figure 21). All recurrences in the placebo group were high-grade, whereas 2 of 4 in the RUTI group were low-grade. Overall RFS rates (calculated including also progression events occurring as the first event) were 55.6% in the placebo group and 78.9% in the RUTI group (p=0.13). High-grade RFS rates (determined by considering only high-grade recurrences and progression events occurring as the first event) were 55.6% and 89.5% (HR=0.295% CI: 0.06-0.7; p=0.02). Significant differences were observed in progression between arms, with progression-free survival rates (PFS) of 72.2% and 100% in the placebo and RUTI® arms, respectively; p=0.015). In terms of event-free survival (EFS), RUTI®-vaccinated patients demonstrated an 80% reduction in the risk of experiencing an event compared to the placebo group (EFS 89.5% and 50% for RUTI® and placebo group, respectively; HR:0.2; 95% CI, 0.06–0.69; p=0.024). No cancer-associated deaths were observed during the 5-year period in RUTI®-vaccinated patients, resulting in a higher cancer-specific free survival rate compared to placebo patients (CSS 100% and 83.3% for RUTI® and placebo group, respectively; p=0.067). Progression to muscle-invasive disease (T2 or greater) occurred in 5 patients, all in the placebo group (27.7%), with 3 progressing as the first event. Cancer-specific deaths occurred in 3 placebo patients (16.7%). See Figure 21 Table 11. Patient outcomes at 5 years follow-up In the high-grade T1 cohort (see Table 6), the differences between groups were further confirmed. RFS rates were 54.5% (placebo) vs 80% (RUTI), high-grade RFS rates were 54.5% vs 90% (p=0.1, HR=0.2, 95% CI=0.04–0.99). Progression and cancer-specific deaths occurred only in the placebo group, leading to significantly higher PFS (63.6% vs.100%, p=0.04) and CSS rates (81.8% vs.100%, p=0.17) in the RUTI group (Fig.23). Two low-grade recurrences in the RUTI group were not classified as BCG failures under EAU guidelines (Gontero, P. et al. European Association of Urology Guidelines on Non–muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)—A Summary of the 2024 GuidelinesUpdate. Eur Urol (2024) doi:10.1016 / j.eururo.2024.07.027). One RUTI patient developed a contralateral ureteric tumor (month 57), classified as a metachronous tumor rather than a local recurrence. Two patients (one from each group) died from unrelated causes. Patients with recurrence or progression were treated with BCG reinduction, radical cystectomy,chemotherapy or immunotherapy according to EAU guidelines (Gontero, P. et al. EuropeanAssociation of Urology Guidelines on Non–muscle-invasive Bladder Cancer (TaT1 andCarcinoma In Situ)—A Summary of the 2024 Guidelines Update. Eur Urol (2024)doi:10.1016 / j.eururo.2024.07.027) (see Figure 21). This is the first clinical trial investigating a heterologous prime–boost strategy to enhance intravesical BCG efficacy in bladder cancer patients. Our data indicate that RUTI® prevents BCG-induced Treg expansion, potentially improving efficacy. RUTI® also generated a broader, more polyfunctional T cell response, with elevated polyfunctional T cells through BCG maintenance. RUTI® effectively primed a systemic BCG-specific immune response, increasing heterogeneous PPD-specific CD4+ and CD8+ T cells prior intravesical BCG. This phase I trial demonstrated that RUT®I vaccination prior BCG therapy is safe, well tolerated, and enhances the immune response. In addition, the data show an improvement in survival by boosting BCG-induced immunity. BCG’s ability to prevent progression remains controversial (Gontero, P. etal. The Role of Bacillus Calmette-Guérin in the Treatment of Non-Muscle-Invasive BladderCancer. European Urology vol. 57 410–429 Preprint athttps: / / doi.org / 10.1016 / j.eururo.2009.11.023 (2010); SYLVESTER, R. J., van der MEIJDEN, A. P. M. & LAMM, D. L. Intravesical Bacillus Calmette-Guerin Reduces the Risk of Progression in Patients with Superficial Bladder Cancer: A Meta-analysis of the Published Results of Randomized Clinical Trials. Journal of Urology 168, 1964–1970 (2002)), but RUTI®’s effect on early recurrences aligns with reduced progression risk, a key mortality predictor in high-risk NMIBC patients. RUTI® also offers a potential cost advantage by reducing recurrence and progression, lowering bladder cancer treatment costs—the highest per-patient cost of any cancer (Walia, A. S., Sweis, R. F., Agarwal, P. K., Kader, A. K. & Modi, P. K. Cost-effectiveness of immune checkpoint inhibitors in urothelial carcinoma—a review. Cancers (Basel) 14, (2022); Rieger, C. et al. Cost-effectiveness analysis of different treatment modalities in BCG- unresponsive NMIBC. BJU Int (2024) doi:10.1111 / bju.16332; Joyce, D. D., Sharma, V. & Williams, S. B. Cost-Effectiveness and Economic Impact of Bladder Cancer Management: An Updated Review of the Literature. Pharmacoeconomics 41, 751–769 (2023)). CLAIMS1. A liposome formulation comprising:(a) fragments from a Mycobacterium tuberculosis-complex (MTB-C) strain,(b) a liposome forming agent, and (c) 1 to 20 % (w / v) sucrose, wherein the z-average size of the particles is 150 nm or less, as determined by dynamic light scattering and the polydispersity index of the particles is 0.400 or less, for use in a method of treating cancer in a human subject.2. The liposome formulation for use in a method of treatment according to claim 1,wherein the Mycobacterium tuberculosis-complex (MTB-C) strain is a virulent Mycobacteriumtuberculosis-complex (MTB-C) strain, preferably the MTB-C strain NCTC (National Colletion of Type Cultures) 13536, deposited in 2010 at the NCTC in London.3. The liposome formulation for use in a method of treatment according to any one ofclaims 1 or 2, additionally comprising (a) a tensioactive agent, and / or (b) one or more non-ionic surfactants.4. The liposome formulation for use in a method of treatment according to any one ofthe preceding claims, wherein the liposome forming agent is a hydrogenated, partially hydrogenated or non-hydrogenated phospholipid, preferably wherein the liposome forming agent is soy lecithin.5. The liposome formulation for use in a method of treatment according to any one ofthe preceding claims, wherein the liposome formulation comprises at least two of the following polypeptides:

Claims

(a) a polypeptide having a molecular weight of about 38 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis 38 kDaprotein (Rv 0934), (b) a polypeptide having a molecular weight of about 30-34 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis Ag85complex protein (Rv 1866c – Rv 3804c), (c) a polypeptide having a molecular weight of about 16 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis HSP 16.3protein (Rv2031c), (d) a polypeptide having a molecular weight of about 10 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis CFP10protein (Rv3874), and (e) a polypeptide having a molecular weight of about 6 kDa as measured following electrophoresis on a sodium dodecylsulfate (SDS) polyacrylamide gel, wherein thepolypeptide has a mass fingerprint similar to a mass fingerprint of M. tuberculosis ESAT-6protein (Rv3875).

6. A pharmaceutical composition comprising the liposome formulation as defined in anyone of the preceding claims and a pharmaceutically acceptable carrier or diluent, and / or a pharmaceutically acceptable adjuvant, for use in a method of treating cancer in a human subject.

7. The liposome formulation or pharmaceutical composition for use according to any oneof claims 1-6, wherein the cancer is a Bacillus Calmette-Guérin (BCG)-responsive cancer, preferably selected from: (i) bladder cancer, wherein preferably the cancer has been resected before said treatment, (ii) melanoma, and(iii) breast cancer.

8. The liposome formulation or pharmaceutical composition for use according to claim 7(i), wherein the bladder cancer is non-muscle-invasive bladder cancer (NMIBC), preferably high-risk NMIBC, wherein the pathological stage is preferably T1 or Ta, optionally associatedto carcinoma in situ (CIS).

9. The liposome formulation or pharmaceutical composition for use according to any oneof the preceding claims, wherein the liposome formulation is administered to the patient twice and wherein preferably, the second dose is administered 5-30 days after the first dose, such as 7-28 days after the first dose, preferably 7–10 days after the first dose, preferably 10 days after the first dose.

10. The liposome formulation or pharmaceutical composition for use according to of any one of the preceding claims, wherein the administration of said formulation is parenteral, preferably subcutaneous.

11. The liposome formulation or pharmaceutical composition for use according to any one of the preceding claims, wherein the treatment is therapeutic cancer vaccination, preferably prime-boost vaccination, more preferably heterologous prime-boost vaccination.

12. The liposome formulation or pharmaceutical composition for use according to claim 11, wherein the therapeutic cancer vaccination is a heterologous prime-boost vaccination, wherein the prime-boost vaccination comprises treatment with the liposome formulation as defined in claim 1 and with Bacillus Calmette-Guérin (BCG), and wherein preferably, the prime vaccine is the liposome formulation as defined in claim 1 and the boost vaccine is BCG.

13. The liposome formulation or pharmaceutical composition for use according to claim 12, wherein the treatment with BCG comprises i) an induction course, wherein BCG is administered six times in weekly intervals and, optionallyii) a maintenance course, wherein BCG is administered in three courses at three, six, and twelve months after the induction course as described in i) wherein optionally, the administration of BCG is intravesical and / or wherein optionally, each dose of BCG comprises 2–8 x 108colony forming units, optionally diluted in 50 mL sterile solution, wherein optionally, the liposome formulation is applied before treatment with BCG, wherein optionally, the last dose of the liposome formulation is administered 3 to 30 days before the day of the first treatment with BCG, preferably 6 to 15 days before the day of the first treatment with BCG, most preferably six days before the day of the first treatment with BCG.

14. The liposome formulation or pharmaceutical composition for use in a method of treatment according to any one of the preceding claims, wherein the liposome formulation orpharmaceutical composition is administered at a dose of 5–200 μg of Mycobacteriumtuberculosis cell wall fragments (FCMtb) per dose, preferably at a dose of 25 µg FCMtb per dose.

15. The liposome formulation or pharmaceutical composition for use according to any one of claims 1-14, wherein the treatment comprises: i) Subcutaneous administration of 5–200 μg of FCMtb, preferably 25 µg of FCMtbto a patient diagnosed with a BCG-responsive cancer, preferably bladder cancer, more preferably NMIBC, even more preferably high-risk NMIBC; ii) Subcutaneous administration of 5–200 μg of FCMtb, preferably 25 µg of FCMtbto the patient, wherein the administration takes place from 5 to 30 days, such as from 7 to 28 days, preferably from 7 to 10 days after the administration of i), preferably 10 days after the administration described in i); iii) Intravesical administration of a BCG induction course, wherein BCG is administered six times in weekly intervals, preferably wherein each dose of BCG comprises 2– 8 x 108colony forming units, wherein the first BCG dose is administered 3 to 30 days after the administration of ii), preferably 6 to 15 days after the administration of ii), even more preferably six days after the administration described in ii); andiv) Intravesical administration of a BCG maintenance course, wherein BCG is administered in three courses at three, six, and twelve months after the induction course described in iii), preferably wherein each dose of BCG comprises 2–8 x 108colony forming units.ABSTRACT The present invention relates to a therapeutic agent based on cell wall fragments of a virulentstrain of Mycobacterium tuberculosis-complex for use in the treatment of cancer.

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