teleukin (F16-IL2) / Philogen - LARVOL DELTA

The role of TNC in atherosclerosis and drug development opportunities. (PubMed, Int J Biol Sci) - "The F16-conjugate agent F16IL2 is undergoing clinical trials...Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia

Clinical advances in TNC delivery vectors and their conjugate agents. (PubMed, Pharmacol Ther) - "G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials...RDCs investigated in clinical trials include In-DTPA-BC-2, I-BC-2, I-BC-4, Y-BC4, I81C6, I-ch81C6, At-ch81C6, F16I, I-tenatumomab, ST2146biot, FDC I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC."

Journal • Review • Oncology • IL12A • IL2

A Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Very Low-dose Cytarabine in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=30 | Terminated | Sponsor: Philogen S.p.A. | Trial completion date: Sep 2022 ➔ Sep 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2022 ➔ Sep 2023; New agents for the same indication impacted on patients' recruitment

Combination therapy • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

A Phase I Trial of the Antibody-Cytokine Fusion Protein F16IL2 in Combination with Anti-CD33 Immunotherapy for Posttransplant AML Relapse (ASH 2021) - "In this novel-novel combination dose-escalation phase 1 trial, we enrolled patients with AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of F16IL2, an antibody-cytokine fusion protein composed of the human antibody fragment scFv(F16) in diabody format and two molecules of human IL-2, in combination with the Fc-optimized, ADCC-mediating anti-CD33 monoclonal antibody BI 836858. In the difficult-to-treat situation of posttransplant AML relapse, responses were observed at higher DL, even in patients with extramedullary disease. The antibody-mediated targeted delivery of IL-2 to the ECM combined with anti-CD33 immunotherapy represents an innovative experimental approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse."

Combination therapy • P1 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Respiratory Diseases • Transplantation • IL2

Nivokin: F16IL2 in Combination With Nivolumab in Patients With Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=3 | Active, not recruiting | Sponsor: Philogen S.p.A.

Combination therapy • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse. (PubMed, Blood Adv) - "ECM-targeted IL-2 combined with anti-CD33 immunotherapy represents an innovative approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. This trial was registered at EudraCT (2015-004763-37)."

Journal • P1 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Respiratory Diseases • Transplantation • IL2

A Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Very Low-dose Cytarabine in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2019 ➔ Sep 2022 | Trial primary completion date: Mar 2019 ➔ Sep 2022

Combination therapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

PHIBI: Trial to Find and Investigate a Safe Dose of F16IL2 and BI 836858 in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Philogen S.p.A. | Recruiting ➔ Completed | N=52 ➔ 15

Combination therapy • Enrollment change • Trial completion • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Combination Therapy of F16IL2 and Paclitaxel in Solid Tumour Patients (clinicaltrials.gov) - P1/2 | N=48 | Completed | Sponsor: Philogen S.p.A. | Recruiting ➔ Completed | N=96 ➔ 48

Enrollment change • Trial completion • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Combination Therapy of F16IL2 and Paclitaxel in Solid Tumour Patients (clinicaltrials.gov) - P1/2; N=96; Recruiting; Sponsor: Philogen S.p.A.; N=51 ➔ 96

Clinical • Combination therapy • Enrollment change • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Phase I study of F16IL2 antibody-cytokine fusion with very low-dose araC in acute myeloid leukaemia relapse after allogeneic stem cell transplantation. (PubMed, Br J Haematol) - No abstract available

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Ying and Yang of Stat3 in pathogenesis of aortic dissection. (PubMed, J Cardiol) - "Therefore, STAT3 regulates the balance between the destruction and the reinforcement of the aortic tissue, depending on the cell types and the time course of STAT3 activation, which ultimately regulates the development of AD. Elucidating such a dynamic mechanism to regulate the aortic tissue integrity would be essential to decipher the molecular pathogenesis of AD."

Journal • Review • Inflammation • IL6 • STAT3

[VIRTUAL] THE ASSOCIATION OF RACE, ETHNICITY, AND OUTCOMES OF PATIENTS WITH COVID-19 IN NEW YORK CITY (CHEST 2020) - "Regarding treatments, both groups had similar treatments such as hydroxychloroquine, azithromycin, steroids, tocilizumab, non-invasive positive pressure ventilation and invasive mechanical ventilation. We reported the detailed description of clinical characteristics with the association of race/ethnicity in the diverse urban population of New York City. CLINICAL IMPLICATIONS: Our study describes the diversity of COVID-19 patient characteristics as well as the population it impacts in New York City. Notably, we investigated the association of race/ethnicity, homelessness, and insurance status (potential surrogate for access to healthcare), which showed non-significant differences between white group and non-white group."

Clinical • Infectious Disease • Novel Coronavirus Disease • IL6

Genetic contributors and soluble mediators in prediction of autoimmune comorbidity. (PubMed, J Autoimmun) - "Emerging soluble biomarkers for SS related lymphoma include mediators of B cell growth and germinal center formation such as BAFF, FMS-like tyrosine kinase 3 ligand (Flt-3L) and CXCL13 as well as inflammatory contributors such as inteleukin (IL)-17, IL-18, ASC, LILRA3 and the extracellular lipoprotein-associated phospholipase A2 (Lp-PLA2). In regard to fatigue and neuropsychologic features in the setting of SS, contributing factors such as BAFF variants, antibodies against neuropeptides, proteins involved in nervous system function as well as inflammatory cytokines have been reported."

Biomarker • Journal • Review • Atherosclerosis • Cardiovascular • Complement-mediated Rare Disorders • Dyslipidemia • Fatigue • Hematological Malignancies • Immunology • Lupus • Psychiatry • Sjogren's Syndrome • Systemic Lupus Erythematosus

Prognostic value of CD25/CD123 pattern of expression in acute myeloid leukemia patients with normal cytogenetic. (PubMed, Leuk Res Rep) - "Identification of CD25/CD123 expression in CN-AML patents at diagnosis could be included in risk stratification. There is strong association between CD25+/CD123+ positive expression and FLT3 mutations."

Clinical • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD123 • FLT3 • IL2 • IL2RA • NPM1

A Nutritional Supplement (DìLsh) Improves the Inflammatory Cytokines Response, Oxidative Stress Markers and Clinical Signs in Dogs Naturally Infected by Leishmania infantum. (PubMed, Animals (Basel)) - "A decrease in d-Roms and an increase in BAP were also detected in both groups. On the whole, the nutritional supplement possesses anti-inflammatory and antioxidant properties, suggesting that it may support animals' health and be useful to extend the time a drug therapy is needed."

Clinical • Journal • Immune Modulation • Inflammation • IL10 • IL6 • LEP • TNFA

Effects of 12-week Aerobic Exercise on Arterial Stiffness, Inflammation, and Cardiorespiratory Fitness in Women with Systemic LUPUS Erythematosus: Non-Randomized Controlled Trial. (PubMed, J Clin Med) - "...At baseline and at week 12, arterial stiffness was assessed through pulse wave velocity (PWV), inflammatory (i.e., high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TFN-α], and inteleukin 6 [IL-6]) and oxidative stress (i.e., myeloperoxidase [MPO]) markers were obtained from blood samples, and cardiorespiratory fitness was assessed (Bruce test)...In comparison to the control group, the exercise group significantly increased cardiorespiratory fitness (median difference 2.26 minutes, 95% CI 0.98 to 3.55; p = 0.001). These results suggest that 12 weeks of progressive treadmill aerobic exercise increases cardiorespiratory fitness without exacerbating arterial stiffness, inflammation, or oxidative stress in women with SLE."

Clinical • Journal • Biosimilar • Cardiovascular • Dyslipidemia • Immunology • Lupus • Systemic Lupus Erythematosus

Flecainide Acetate Attenuates Endotoxin Induced Acute Lung Injury in Rats by Controlling Inflammatory Response (ASA 2016) - "Rats were sacrificed for analyses of severity of acute lung injury involving wet to dry (W/D) ratio and lung injury score (LIS) in lung and inflammatory responses involving level of leukocyte, polymorphonuclear neutrophils (PMNs) and inteleukin-8 (IL-8) in bronchoalveolar lavages fluid (BALF). Flecainide acetate markedly attenuated dose dependently endotoxin-induced lung injury as determined by W/D ratio (from 2.24±0.11 to 1.76±0.09, p<0.05) and LIS (from 3 to 1, p<0.05), and inflammatory response as determined by leukocyte (from 443±127 to 229±95, p<0.05), PMNs (from 41.43±17.63 to 2.43±2.61, p<0.05) and IL-8 (from 95.00±15.28 to 40.00±10.21, p<0.05) in BALF. Flecainide acetate attenuates endotoxin induced acute lung injury by dose-dependent manner in rats by controlling inflammatory responses."

Preclinical • Biosimilar • Cardiovascular

NEUROPROTECTIVE ROLE OF KOLAVIRON IN STRIATAL REDO-INFLAMMATION ASSOCIATED WITH ROTENONE MODEL OF PARKINSON'S DISEASE. (PubMed, Neurotoxicology) - "KV-treated rats showed improved capacity to maintain efficient gait with minimal rigidity and enhanced coordination. Taken together, kolaviron exhibited neuroprotective properties, which may be beneficial for the prevention and management of Parkinson's disease, via antioxidant, anti-inflammatory and anti-apoptotic mechanisms."

Journal

Off-label Use of Tocilizumab in Patients with SARS-CoV-2 Infection. (PubMed, J Med Virol) - "Particularly, no approved therapy has demonstrated to have an impact in treating patients who develop severe respiratory insufficiency so far. The use of humanized anti-human inteleukine-6 receptor antibody tocilizumab seems a promising strategy for these patients."

Clinical • Journal • Immunology • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Impact of Resistance Training Program Configuration on the Circulating Brain-Derived Neurotrophic Factor Response. (PubMed, Appl Physiol Nutr Metab) - "A minimum volume threshold of RT may be needed to induce acute elevations in BDNF. Novelty • A minimum RT volume threshold may be needed to elicit BDNF • A close proximity to failure may be needed to elicit BDNF • BDNF and IL-6 did not correlate."

Journal • BDNF • IL6

Cardiac Metastasis in a Patient with Clear Cell Renal Cell Carcinoma who Underwent Multimodality Therapy for Multiple Metastases after Radical Nephrectomy (PubMed, Hinyokika Kiyo) - "Nivolumab was administered for cardiac metastases. The patient has been in stable condition with no progression of cardiac metastases after the administration of nivolumab for 22 months."

Clinical • Journal

Role of biomarkers of acute kidney damage during lithotripsy of high-density stones (PubMed, Urologiia) - "Our study proves that IL-18, NGAL, leukocyte migration inhibition test and selective proteinuria allows to diagnose AKI at early stages, as well as to objectively assess the functional state of the kidneys after lithotripsy. The obtained data proves that laser lithotripsy is the safest method as assessed by damaging effects on the kidney parenchyma."

Biomarker • Journal

Innate Immune Modulation by GM-CSF and IL-3 in Health and Disease. (PubMed, Int J Mol Sci) - "Granulocyte-macrophage colony-stimulating factor (GM-CSF) and inteleukin-3 (IL-3) have long been known as mediators of emergency myelopoiesis, but recent evidence has highlighted their critical role in modulating innate immune effector functions in mice and humans...Finally, GM-CSF and to a lesser extent IL-3 play a critical role in experimental models of trained immunity by acting not only on bone marrow precursors but also directly on mature myeloid cells. Altogether, characterizing GM-CSF and IL-3 as central mediators of innate immune activation is poised to open new therapeutic avenues for several immune-mediated disorders and define their potential in the context of immunotherapies."

Journal • Review