picibanil (OK-432) / Roche - LARVOL DELTA

Concentration-dependent effects of immunomodulatory cocktails on the generation of leukemia-derived dendritic cells, DCleu mediated T-cell activation and on-target/off-tumor toxicity. (PubMed, Front Immunol) - "Such protocols combine approved response modifiers (i.e., GM-CSF and PGE1/OK-432/PGE2) that synergistically improve the conversion of AML blasts into (mature) DC/DCleu...In conclusion, our results highlight that Kit-mediated DC/DCleu generation, immune cell activation and blast lysis are dependent on the concentration of response modifiers, which will guide future clinical development. Overall, DCleu-based immunotherapy represents a promising treatment strategy for AML patients."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CSF2

Coactivation of innate immune suppressive cells induces acquired resistance against combined TLR agonism and PD-1 blockade. (PubMed, Sci Transl Med) - "The accumulation of PMN-MDSCs was similarly observed in the pleural effusions of patients with lung cancer after OK-432 administration. We propose that successful combination cancer immunotherapy intended to stimulate innate antitumor immunity requires modulation of unwanted activation of innate immune suppressive cells, including PMN-MDSCs."

Journal • Preclinical • Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • CD8 • CXCL1 • CXCR2

Treatment of Secondary Spontaneous Pneumothorax due to Tumor Rupture:Report of a Case (PubMed, Kyobu Geka) - "The patient underwent a subsequent pleurodesis with picibanil. This case illustrates the challenges, which emphasize the need for alternative air leak management strategies when resection is not feasible."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor

Multidisciplinary therapeutic strategy with appropriate timing and modalities for treating cervicofacial lymphatic malformations in children. (PubMed, Pediatr Surg Int) - "The study concluded that early sclerotherapy for infants, particularly around the airway, poses risks, and tracheostomy might be necessary. The comprehensive strategy including "wait-and-see," sclerotherapy, sirolimus treatment, and timely surgery significantly improved the patients' quality of life."

Journal • Retrospective data

Duodenal Lymphangioma Presenting as a Duodenal Polyp: A Rare Entity (ACG 2024) - "Even though they have no malignant potential, they have a strong tendency for recurring and hence need to be completely excised. Non-surgical treatments include sclerosing agent like OK 432 (Picibanil) which has been used in eradication of small tumors."

Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Dyspepsia • Fatigue • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Metabolic Disorders • Nephrology • Oncology • Pain • Pediatrics • Pulmonary Disease • Renal Disease • Solid Tumor • Type 2 Diabetes Mellitus

Microembolization effects of imipenem/cilastatin in vivo Depicted by Monochromatic Synchrotron X-ray Microangiography. (PubMed, J Vasc Interv Radiol) - "IPM/CS exhibited an ultra-short embolic effect not seen with existing embolic materials and may have a long embolic effect specific to inflamed vessels rather than normal vesseles. This characteristic could contribute to the indications for embolization being expanded to new diseases, such as embolization for pain relief in chronic joint pain."

Journal • Preclinical • Anesthesia • Inflammation • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain

ADVANCED-2: PHASE 2 OPEN-LABEL STUDY TO EVALUATE SAFETY AND ANTI-TUMOR ACTIVITY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (SUO 2024) - P2 | "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications... Preliminary data from the ADVANCED-2 study suggests that TARA-002 appears to be well tolerated, thus demonstrating a favorable tolerability profile for the treatment of BCG Naïve and BCG unresponsive subjects with CIS (±Ta/T1) NMIBC. Enrollment is ongoing and updated data will be shared at the time of the presentation."

Clinical • Metastases • P2 data • Genito-urinary Cancer • Immunology • Infectious Disease • Nephrology • Oncology • Solid Tumor • Urinary Incontinence • Urology

PHASE I CLINICAL TRIAL OF ADJUVANT THERAPY UTILIZING SIX TUMOR-ASSOCIATED ANTIGEN-DERIVED PEPTIDES AND AUTOLOGOUS DENDRITIC CELLS FOR HEPATOCELLULAR CARCINOMA (AASLD 2024) - " Monocyte-derived autologous dendritic cells pulsed with six antigen peptides (SART2889, SART3109, MRP3765, AFP403, AFP357, hTERT461) were prepared as regenerative medical products using GM-CSF, IL-4, and OK-432, then subcutaneously administered three times at 2-week intervals to patients with hepatocellular carcinoma who underwent RFA... We confirmed the feasibility, safety, and induction of immune responses with dendritic cell vaccination with six tumor-associated antigen-derived peptides. Future studies will involve further clinical trials testing the efficacy of the treatment."

Clinical • P1 data • Cardiovascular • Fatigue • Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Ischemic stroke • Oncology • Solid Tumor • CSF2 • IFNG • IL4

Rare Yet Relevant: Adult Onset Cervical Lymphangioma - Our Experience and Comprehensive Review. (PubMed, Indian J Otolaryngol Head Neck Surg) - "A 6 -month follow-up in all 15 cases showed no recurrences. Overall, this study underscores the importance of a multidisciplinary approach involving clinicians, radiologists, and surgeons in the management of adult cervical lymphangiomas, with an emphasis on accurate diagnosis, appropriate classification, and tailored treatment strategies to optimize patient outcomes and minimize complications."

Journal • Review • Gastrointestinal Disorder • Oncology • Otorhinolaryngology • Pain • Pulmonary Disease

Comparison between OK-432 and Talc for pleurodesis in patients with persistent pulmonary air leak: a Japanese nationwide retrospective database study. (PubMed, Gen Thorac Cardiovasc Surg) - "Medical professionals can consider talc as the initial pleurodesis agent for patients with persistent air leaks."

Journal • Retrospective data • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo. (PubMed, Mol Immunol) - "Kit-M (granulocyte-macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) were used to generate leukemia derived APC/DC (DCleu)from WB, which were subsequently used to stimulate T-cell enriched MLC...We also found higher frequencies of TCRγδ expressing T-cells in AML patients´ samples with an achieved remission (compared to blast persistence) after induction chemotherapy. This might point to APC/DC-mediated effects resulting in the provision of leukemia-specific TCRγδ expressing T-cells: Moreover a quantification of TCRγδ expressing T-cells might contribute to predict prognosis of AML/MDS patients."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • APC • CSF2

Efficacy and mechanism of percutaneous injection of group A streptococcal preparations in the treatment of simple renal cysts (ChiCTR) - P=N/A | N=180 | Recruiting | Sponsor: The First Affiliated Hospital,Sun Yat-sen University; The First Affiliated Hospital,Sun Yat-sen University

New trial

Phase 3 Trial of Pleurodesis for Malignant Pleurisy: Sterile Graded Talc vs. OK-432 WJOG8415L (J-PLEURA) (IASLC-WCLC 2024) - "Both treatments had equivalent safety outcomes and similar impacts on QoL. While OK-432's insignificant advantage in non-recurrence survival rates over three months positions it as a viable option, the singular treatment-related death necessitates cautious interpretation, although it does not undermine its overall efficacy comparable to that of talc."

P3 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Infectious Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor

TLR agonists promote formation of Tertiary Lymphoid Structure and improve anti-glioma immunity. (PubMed, Neuro Oncol) - "TLS induction in GME enhanced anti-glioma immunity, improved the immune microenvironment, and controlled glioma growth, suggesting potential therapeutic avenues for treating glioma in the future."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • CD4 • CD8 • TLR2

Sclerotherapy vs. surgical excision for lymphatic malformations of the head and neck: a systematic review and meta-analysis. (PubMed, Eur Arch Otorhinolaryngol) - "Both surgical excision and STS combined with ethanol are highly effective for treating macrocystic LMs, achieving similar complete response rates. The combination of sclerotherapy and surgical excision demonstrated the best outcomes in microcystic LMs. Surgical excision demonstrates superior efficacy over sclerotherapy for mixed LMs. These findings suggest that excision is generally more effective in achieving complete and excellent responses across all LM subtypes. Further high-quality studies are necessary to standardize and optimize treatment protocols."

Journal • Retrospective data • Review

Simultaneous activation of innate immune suppressive components impairs antitumor efficacy of immunotherapy against the innate immune system (AACR 2024) - "We then employed OK-432, which reportedly stimulates TLR-2, TLR-4, and/or TLR-9, as OK-432 is widely used in Japan in the clinic...Taken together, we propose that successful combination treatment stimulating innate immunity against immunogenically cold cancers requires controlling the unwanted co-activation of innate immune suppressive cells. This study clearly demonstrates the mechanism of acquired resistance after administration of reagents that activate innate immunity, such as TLR agonists or STING agonists, and provides the basis for future successful combination therapy."

Clinical • Oncology • CXCL1 • CXCR2 • TLR4 • TLR9

Radiofrequency hyperthermia enhances the effect of OK-432 for Hepatocellular carcinoma by activating of TLR4-cGAS-STING pathway. (PubMed, Int Immunopharmacol) - "The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TLR4

Effectiveness of pleurodesis for postoperative air leaks after lung resection. (PubMed, J Cardiothorac Surg) - "The efficacies of autologous blood patch, talc, and OK-432 would be considered comparable and early postoperative pleurodesis could shorten drainage time. Prospective studies are required."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pleurodesis using OK-432 for persistent pleural effusion after cardiac surgery in the neonatal period or early infancy. (PubMed, Asian Cardiovasc Thorac Ann) - "Pleurodesis using OK-432 is effective and reliable for persistent postoperative pleural effusion in neonates and early infants. Most of the complications, which derived from inflammatory reactions, were temporary and controllable. However, severe lymphedema is difficult to control."

Journal • Pleural effusion • Surgery • Atrial Fibrillation • Cardiovascular • Infectious Disease • Inflammation • Pediatrics • Respiratory Diseases • Septic Shock

PHASE 1B/2 DOSE-EXPANSION, OPEN-LABEL STUDY TO EVALUATE SAFETY AND ANTI-TUMOR ACTIVITY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (SUO 2023) - P1b/2 | "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications...The study duration per subject is 6 months for Cohort A and 24 months for Cohort B. Phase 1b/2 is currently open for enrollment. "

Clinical • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ADVANCED-1: PHASE 1A DOSE-FINDING, OPEN-LABEL STUDY TO EVALUATE SAFETY AND TOXICITY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (SUO 2023) - "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC via intravesical instillation. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications... In the ADVANCED-1 study, TARA-002 was generally well tolerated at all three evaluated dose levels and thus demonstrated a favorable safety profile for the treatment of high-grade NMIBC. A MTD was not determined, and dose escalation remains ongoing in exploratory Phase 1a cohorts. Furthermore, anti-tumor activity was observed at 20 KE and 40 KE."

Clinical • Metastases • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Pain • Solid Tumor

Synergistic Effect of OK-432 in Combination with Anti-PD-1 Antibody for Residual Tumors after Radiofrequency Ablation of Hepatocellular Carcinoma (RSNA 2023) - "The combined therapy of OK-432 with αPD-1 antibody induced a strong anti-tumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. *Clinical Relevance/Application: This concept may provide a new strategy to increase the curative efficacy of RFA for medium-to-large or irregular HCCs."

Combination therapy • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • FOXP3

Elucidation of the Microvascular Embolization Effects of Imipenem/Cilastatin¦ Evaluation at the Level of Microvessels using Monochromatic X-ray in Vivo Study (RSNA 2023) - "A portion of one ear of each rabbit was injected subcutaneously with picibanil (0.5 KE) to create an inflammation-induced model. The characteristics of IPM/CS as an embolic material in vivo were elucidated. In vivo, much larger vessels are embolized than the actual particle size. It was also suggested that the embolization effect duration might differ between normal and inflammation-induced areas."

Preclinical • Anesthesia • Immunology • Inflammation • Pain • Rheumatology

STING Pathway Activation and Antitumor Immunity Induction by an Injectable Hydrogel Loaded Lysed OK-432 and DOX for Incomplete Radiofrequency Ablated Liver Cancer (RSNA 2023) - "*Purpose: To investigate the efficacy and mechanism of an injectable hydrogel loaded lysed OK-432 and doxorubicin for incomplete radiofrequency ablated (inRFA) liver cancer. The novel ROD peptide hydrogel was effective for the treatment of liver cancer previously treated with inRFA. *Clinical Relevance/Application: This modality probably leads to a progression in the eradication of larger liver cancer in clinical practice."

Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNB1 • IFNG • STING • TNFA

Non-invasive Radiofrequency Hyperthermia Enhances the Effect of OK-432 for Hepatocellular Carcinoma Via Activation of cGAS-STING Pathway (RSNA 2023) - "Furthermore, this combined treatment resulted in a better tumor response and a prolonged survival. In conclusion, the combination therapy might be a new treatment strategy in reducing the residual tumor after RFA of medium-to-large or irregular HCCs, bringing a new option for other types of malignancies treated by RFA."

Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • IFNB1 • TLR4