bacillus Calmette-Guerin (BCG) / Lacocca Family Foundation - LARVOL DELTA

Diabetic Immunotherapy Advances with BCG: Metabolic and Immune Reprogramming. (PubMed, Cells) - "BCG's consistent clinical benefits in autoimmune diabetes coincide with the gradual pace of upstream epigenetic reprogramming of genes involved in metabolic and T cell pathways without changing genotype. Understanding the mechanistic chain linking BCG-induced epigenetic changes to clinical efficacy may offer insights into the treatment and potential prevention of autoimmune diabetes."

IO biomarker • Journal • Review • Bladder Cancer • Diabetes • Genito-urinary Cancer • Immunology • Infectious Disease • Metabolic Disorders • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Tuberculosis • Type 1 Diabetes Mellitus

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926. (PubMed, J Clin Oncol) - "Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy."

Journal • P2 data • Bladder Cancer • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Urothelial Cancer

Phase II clinical trial testing BCG immunotherapy for latent autoimmune diabetes in adults (LADA): five-year analysis of HbA1c, insulin use and pancreatic C-peptide outcomes (EASD 2026) - P2 | "At Year 5, patients with LADA did not demonstrate significant HbA1c reduction with BCG, but did show improved insulin resistance, slowed C-peptide decay, restored stimulated peak C-peptide, and decreased diabetes-associated autoantibodies, suggesting diminished autoimmunity."

Clinical • P2 data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Phase II clinical trial testing BCG immunotherapy for type 1 diabetes with juvenile onset: five-year analysis of safety, HbA1c, time in range and insulin use (EASD 2026) - P2 | "This study shows that multi-dose BCG is safe and lowers HbA1c, reduces insulin need, and improves time with normoglycemia without increases in hypoglycemic events in adults with juvenile-onset T1D. BCG's therapeutic effect on blood sugar control is independent of pancreas function and is likely a durable correction of an underlying aerobic lymphoid metabolic defect in those with juvenile-onset T1D."

Clinical • P2 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Bacillus Calmette-Guérin (BCG) immunotherapy reprograms CNS immunity and alters Alzheimer's biomarkers: results from two open-label clinical trials. (PubMed, Commun Med (Lond)) - P2 | "These findings suggest trained immunity-like responses in the central nervous system that may influence Alzheimer's-relevant pathways. This approach may represent an early neurodegenerative intervention strategy, although larger controlled studies are needed to confirm these observations."

Biomarker • IO biomarker • Journal • Alzheimer's Disease • CNS Disorders

Repeat BCG Vaccinations for the Treatment of New Onset Type 1 Diabetes in Children Age 8-<18 Years (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: May 2028 ➔ May 2031 | Trial primary completion date: May 2028 ➔ May 2031

Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Repeat BCG Vaccinations For The Treatment Of Pediatric Type 1 Diabetes (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2027 ➔ Mar 2031 | Trial primary completion date: Mar 2027 ➔ Mar 2031

Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Immunology • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus

Phase II Clinical Trial of BCG Immunotherapy for Type 1 Diabetes with Juvenile Onset: Five-Year Analysis of Safety, HbA1c, Time in Range, and Insulin Use (ADA 2026) - P2 | "This study shows that multi-dose BCG is safe and lowers HbA1c, reduces insulin need, and improves time with normoglycemia without increases in hypoglycemic events in adults with juvenile-onset T1D. BCG's therapeutic effect on blood sugar control is independent of pancreas function and is likely a durable correction of an underlying aerobic lymphoid metabolic defect."

Clinical • Late-breaking abstract • P2 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Phase II Clinical Trial of BCG Immunotherapy for Latent Autoimmune Diabetes in Adults (LADA): Five-Year Analysis of HbA1c, Insulin Use, and Pancreatic C-Peptide Outcomes (ADA 2026) - P2 | "At Year 5, patients with LADA did not demonstrate significant HbA1c reduction with BCG, but did show improved insulin resistance, slowed C-peptide decay, restored stimulated peak C-peptide, and decreased diabetes-associated autoantibodies, suggesting diminished autoimmunity."

Clinical • Late-breaking abstract • P2 data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Cyclodextrin-Based Nano-Immunotherapy Enhances Dendritic Cell Activation to Drive Anti-Tumor Immunity in Bladder Cancer (IMMUNOLOGY 2026) - "Introduction/Rationale: High risk non muscle invasive bladder cancer is commonly treated with intravesical BCG therapy, yet many patients fail treatment or develop recurrent disease...Unexpectedly, inclusion of the JAK inhibitor ruxolitinib further enhanced IL-12 production when co-delivered with innate agonists. Bone marrow-derived dendritic cells from IL-12 reporter mice were used to quantify cytokine production following CANDI treatment... Triple combination CANDI is a potent dendritic cell activating nano immunotherapy that drives durable anti tumor immunity and provides a rational strategy to overcome limitations of prior innate immune agonist therapies."

Late-breaking abstract • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Solid Tumor • CD4 • IL12A

INTRATHECAL MYELOID REPROGRAMMING REVEALS CNS SPECIFIC EFFECTS OF BACILLUS CALMETTE–GUÉRIN IMMUNOTHERAPY IN ALZHEIMER'S DISEASE (ADPD 2026) - P2 | "This study provides the first evidence that peripherally administered BCG immunotherapy induces functional remodeling of CNS myeloid cells with compartment-specific effects. These findings, coupled with biomarker changes suggestive of Aβ42 redistribution, offer proof-of-concept for central immune engagement by peripheral immunotherapy and highlight immune training as a potential strategy for early intervention in neurodegeneration."

IO biomarker • Alzheimer's Disease • CNS Disorders • Dementia • Aβ42 • CD4 • GFAP • p-tau181

Impact of BCG Immunotherapy on Plasma p-tau217 in Patients with Type 1 Diabetes at Risk of Alzheimer's Disease: A Five-Year, Phase II, Randomized, Controlled Trial (CTAD 2025) - No abstract available

Clinical • Late-breaking abstract • P2 data • Alzheimer's Disease • CNS Disorders • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Intradermal BCG Immunotherapy Induces Durable Trained Immunity Signatures in CNS Monocytes and Reprograms Neuroimmune Pathways in Aging and Alzheimer's Disease (CTAD 2025) - No abstract available

Alzheimer's Disease • CNS Disorders

Single-cell RNA-sequencing of BCG naïve and recurrent non-muscle invasive bladder cancer reveals a CD6/ALCAM-mediated immune-suppressive pathway. (PubMed, NPJ Precis Oncol) - "These observations were supported by analysis of an independent BCG-treated NMIBC cohort, in which CD6/ALCAM signaling was correlated with shorter recurrence-free survival (p = 0.00059). Our findings reveal a previously unrecognized association between CD6/ALCAM signaling and BCG resistance in NMIBC patients and highlight this pathway as a potential therapeutic target to enhance response to BCG."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

BCG Clinical Trial Programs in Advanced Type 1 Diabetes—2025 Update (ADA 2025) - "BCG can work decades after T1D onset by changing glucose metabolism within lymphocytes, independently of the pancreas. Pediatric trials have the advantage of early age of onset and remaining pancreas function in some cases. BCG vaccine therapy may provide a safe and affordable medical intervention in longstanding T1D."

Clinical • Metastases • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Basal Cell Carcinoma Arising Within a Bacillus Calmette-Guérin Vaccination Scar With Prolonged Inflammatory Response: Case Report. (PubMed, Clin Case Rep) - "Infiltrative basal cell carcinoma (iBCC) can rarely arise within scar tissue, as demonstrated by this unique case of BCC developing in a Bacille Calmette-Guérin (BCG) vaccination scar. This underscores the importance of monitoring prolonged post-vaccination inflammation and exploring its potential link to skin cancer development."

Journal • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer

Summary from the NCI clinical trials planning meeting on next generation of clinical trials in non-muscle invasive bladder cancer. (PubMed, Bladder Cancer) - "The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies. Two clinical trial concepts were developed for potential implementation within the National Clinical Trials Network."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Heterogeneous treatment effects of BCG vaccine on Alzheimer's disease risk. (PubMed, J Alzheimers Dis Rep) - "BCG is associated with a lower risk of ADRD through novel analysis methods and has detected heterogeneity of treatment effects. This presents BCG as a potential low-cost method, with few side-effects, to prevent ADRD."

Heterogeneity • Journal • Alzheimer's Disease • Bladder Cancer • CNS Disorders • Dementia • Genito-urinary Cancer • Oncology • Psychiatry • Respiratory Diseases • Solid Tumor

Phase II Clinical Trial: Multi-dosing the BCG Vaccine for Fibromyalgia (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Massachusetts General Hospital | Trial completion date: Jan 2023 ➔ Jan 2027 | Trial primary completion date: Jan 2023 ➔ Jan 2027

Trial completion date • Trial primary completion date • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Phase II and Phase III RCT Testing Multi-dose BCG Vaccines for Platform COVID-19 and Infectious Disease Protection (Vaccines RD 2024) - No abstract available

P2 data • P3 data • Infectious Disease • Novel Coronavirus Disease

Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques. (PubMed, Cell Syst) - "We find that integrating multiple data modes with MFs helps remove spurious connections. Finally, we used the MF to predict outcomes of perturbations at various immune nodes, including an experimentally validated B cell depletion that induced network-wide shifts without reducing vaccine protection."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Antibodies as key mediators of protection against Mycobacterium tuberculosis. (PubMed, Front Immunol) - "Although the global prevalence of TB has remained high for decades and is an annual leading cause of death attributed to infectious diseases, only one vaccine, Bacillus Calmette-Guérin (BCG), has been approved so far to prevent/attenuate TB disease...Broadening the paradigm of differentiated antibody profiling and antibody-based detection during TB disease progression offers new directions for diagnosis, treatment, and preventative strategies. This approach involves linking the aforementioned humoral responses with the disease state, progression, and clearance."

Biomarker • Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

The spleen assumes a major role in blood glucose regulation in type 1 diabetes patients treated with BCG. (PubMed, Sci Rep) - "The human spleen is significant because its 47% increase in 18F-FDG uptake by a large population of lymphocytes and monocytes might help to explain BCG's systemic lowering of blood glucose to near normal levels. Findings suggest that the spleen, triggered by BCG, assumes a critical role in systemic glucose regulation in the absence of a functional pancreas."

Clinical • Journal • Bladder Cancer • Diabetes • Genito-urinary Cancer • Immunology • Infectious Disease • Metabolic Disorders • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Tuberculosis • Type 1 Diabetes Mellitus

Late in the US pandemic, multi-dose BCG vaccines protect against COVID-19 and infectious diseases. (PubMed, iScience) - "In contrast to the protection afforded by BCG, as reported by others, COVID-19 mRNA vaccine alone provided no protection from COVID-19 disease (p = 0.43). BCG vaccination efficacy was unaffected by concurrent COVID-19 vaccinations; COVID-19 vaccines neither helped nor hindered BCG protection."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases • Type 1 Diabetes Mellitus

Rapid, antibiotic incubation-free determination of tuberculosis drug resistance using machine learning and Raman spectroscopy. (PubMed, Proc Natl Acad Sci U S A) - "We collect few-to-single-cell Raman spectra from over 25,000 cells of the Mtb complex strain Bacillus Calmette-Guérin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin, and amikacin, as well as a pan-susceptible wildtype strain. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5,000. We show how this instrument and our machine learning model enable combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG."

Journal • Machine learning • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis