depletin (CRB 15) / Roche - LARVOL DELTA

Advanced cytokine-based immunotherapies: targeted cis-delivery strategies for enhanced anti-tumor efficacy and reduced toxicity. (PubMed, MAbs) - "This review highlights key common γ-chain cytokines (IL-2, IL-7, IL-15, and IL-21) as well as IL-12, providing an overview of their structures, receptors, as well as their distinct T cell functions. Furthermore, we specifically focus on the current landscape of engineered cytokine variants that facilitate targeted cytokine delivery in cis to specific T cells. By successfully restricting cytokine activity to specific T cell populations, cis-targeting approaches represent a promising strategy in the field, enabling efficient immunotherapies with improved tolerability and enhanced anti-tumor responses."

IO biomarker • Journal • Review • Oncology • IL12A • IL15 • IL21 • IL2RA • IL7

Optimizing Ex-Vivo Expanded NK Cell- Mediated Cellular Cytotoxicity By Obinutuzumab Combined with NKTR-255 in Burkitt Lymphoma (BL) (ASH 2023) - "NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and NK cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells (Kuo/Zalevsky, Cancer Res. We found that NKTR-255 significantly enhanced the ADCC of expanded NK cells with Obinutuzumab against rituximab-resistant BL cells in vitro with enhanced IFN- g, granzyme B and perforin release. The in vivo effects of NKTR-255 with expanded NK cells and Obinutuzumab against rituximab-resistant BL cells using humanized NSG models are very promising. Mechanisms studies of BL relapsed from the combination therapy are under investigation."

IO biomarker • Preclinical • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD8 • GZMA • GZMB • IFNG • IL15 • IL21

Interleukins 15 and 18 synergistically prime the antitumor function of natural killer cells through noncanonical activation of mTORC1. (PubMed, Sci Signal) - "Moreover, both pathways operated independently of the inhibitor TSC and the activator Rheb, revealing a noncanonical mode of mTORC1 activation by cytokines. Treating mice with IL-15 and IL-18 in combination led to increased NK cell numbers and improved antitumoral activity, suggesting that this cytokine combination could be exploited to enhance NK cell potential in therapeutic settings."

Journal • Oncology • IL15 • IL18 • RHEB

IL15/IL15Ra complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to expand progenitor TCF1+ CD8 T cells. (PubMed, Mol Cancer Ther) - "Finally, we show that in the absence of functional IL15 signaling, the immunostimulatory response to RT + PD1-IL2v is significantly diminished with a concurrent lack of TCF+ CD8 T cell generation, suggesting a necessity of IL15 for CD8 stem cells in mediating a durable response to treatment. Together, our results are illustrative of a mechanism wherein unimpeded effector T cell activation through IL2Rb signaling and Treg inhibition are necessary in mediating an anti-tumor immune response."

IO biomarker • Journal • Oncology • CD8 • IL15 • RAG1

Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade. (PubMed, J Immunother Cancer) - "Obese and non-obese patients with cancer have divergent immunological responses to ICIs. Obesity is associated with reduced levels of certain inhibitory cytokines and higher expression of T-cell exhaustion markers. ICI-based therapy may more effectively reverse T-cell dysfunction in obese patients, potentially contributing to the paradoxically improved responses in this population."

Checkpoint inhibition • IO biomarker • Journal • Genetic Disorders • Obesity • Oncology • Solid Tumor • CXCL8 • IL15 • IL6

Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis. (PubMed, Brain Pathol) - "Analysis of 78 inflammatory molecules in paired post-mortem CSF, the levels of fibrinogen (R: 0.640, p = 8.752 x 10-6), PDGF-bb (R: 0.470, p = 0.002), CXCL13 (R: 0.428, p = 0.006) and IL15 (R: 0.327, p = 0.040) were correlated with extent of CP inflammation. Elevated fibrinogen and complement deposition were found in CP and in underlying subependymal periventricular areas, according to "surface-in" gradient associated with concomitant prominent microglia activation. CP inflammation, predominantly characterized by innate immunity, represents another key determinant of intrathecal, compartmentalised inflammation persisting in progressive MS, which may be possibly activated by fibrinogen and influence periventricular pathology, even without substantial association with clinical features."

Journal • CNS Disorders • Infectious Disease • Inflammation • Multiple Sclerosis • CD163 • CXCL13 • IL15 • ITGAX

neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis (MSMilan 2023) - "From the analysis of 78 inflammatory molecules in paired CSF, 4 of them were correlated significantly with CP inflammation: Fibrinogen (R: 0.640, p: 8.752x10-6), PDGF-bb (R: 0.470, p: 0.002), CXCL13 (R: 0.428, p: 0.006) and IL15 (R: 0.327, p: 0.040). Our results suggest a key role of CP inflammation strictly correlated with intrathecal MS inflammation, but is mainly characterized innate immune activity and fibrinogen-complement pattern reactivity."

CNS Disorders • Inflammation • Multiple Sclerosis • CD163 • CXCL13 • IL15 • ITGAX • TREM2

Targeted chain-exchange-mediated reconstitution of a split type-I cytokine for conditional immunotherapy. (PubMed, MAbs) - "We demonstrate that targeted on-cell prodrug conversion is more efficient than nonspecific activation in-solution. Due to the structural similarity between IL-4 and other type I cytokines relevant in cancer immunotherapy such as IL-2, IL-15, and IL-21, cytokine-PACE may be expanded to develop a variety of targeted conditionally active cytokines for cancer immunotherapy."

Journal • Oncology • IL15 • IL2 • IL21 • IL4

"📢#JEMjc Two exciting studies on engineered cytokines in immunotherapy. One by Dr. Pablo Umaña @Roche and colleagues on PD-1-cis IL-2R @Nature https://t.co/ZyAhGb2q13 One by Dr. Yang-Xin Fu @Tsinghua_Uni and colleagues on αPD-1-IL-15-R @JExpMed https://t.co/tcJX8eN5Qm" (@Cindy_JExpMed)

IL15 • IL2RA • PD-1

Optimizing Chimeric Antigen Receptor (CAR) Engineered NK Cell-Mediated Cytotoxicity Combined with Anti-CD20 or Anti-CD79 Therapeutic Antibodies and NKTR-255 in Burkitt Lymphoma (BL) (TCT-ASTCT-CIBMTR 2022) - "Polatuzumab Vedotin (PV) is an anti-CD79 mAb drug conjugate and has demonstrated significant preclinical activity against indolent CD79b+ NHL (Polson, et al, Cancer Res, 2009)...NKTR-255 is an investigational IL-15Rα-dependent, polymer-conjugated, recombinant human IL-15 agonist that retains the full spectrum of IL-15 biology, including expansion of NK cells (Miyazaki, JITC, 2021; Robinson, J Clin Invest, 2021). Objective : To investigate the anti-tumor effect of ex-vivo expanded anti-CD19 CAR NK cells combined with rituximab, Obinutuzumab, or PV with or without NKTR-255 against BL... We found that NKTR-255 + Ritux, Ob or PV significantly enhanced the in vitro cytotoxicity of anti-CD19 CAR NK cells against BL cells. The in vivo effects of NKTR-255 with anti-CD19 CAR NK cells and Ritux, Ob or PV against rituximab-sensitive and -resistant BL cells using humanized NSG models are under investigation. (This work is funded by Children’s Cancer Fund Laboratory at New York..."

Burkitt Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Oncology • CD79B • GZMB • IFNG

Risk assessment of latent tuberculosis infection through a multiplexed cytokine biosensor assay and machine learning feature selection. (PubMed, Sci Rep) - "The reduced set for increased risk included IP-10, IL-2, IFN-γ, TNF-α, IL-15, IL-17, CCL3, and CCL8 under varying normalized stimulation conditions. ROC curves determined predictive accuracies of > 80% for both LTBI diagnosis and increased risk designations. Our study findings suggest that a multiparameter diagnostic approach to detect normalized cytokine biomarker signatures might improve risk stratification in LTBI."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CCL3 • IFNG • IL15 • IL17A • IL2 • TNFA

[VIRTUAL] COVID-19 Prognosis in Patients with Underlying CKD and Kidney Related Complications (ATS 2021) - " Retrospective chart review including patients aged 18 years and older, admitted to a community hospital from March 15; 2020 to April 15; 2020, testing positive for COVID-19... Early renal involvement and underlying CKD worsen the prognosis of COVID-19 pneumonia and result in higher mortality outcomes. Such patients, especially those with findings of hematuria on admission, need closer monitoring. Furthermore, many COVID-19 patients receive steroids and anticoagulants as part of treatment regimen which will need to be further evaluated as these therapies may contribute to further damage of the kidneys."

Clinical • Acute Kidney Injury • Chronic Kidney Disease • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pneumonia • Renal Disease • Respiratory Diseases

Assessment of Cumulative Incidence and Severity of Primary Open-Angle Glaucoma Among Participants in the Ocular Hypertension Treatment Study After 20 Years of Follow-up. (PubMed, JAMA Ophthalmol) - P3 | "From January 7, 2016, to April 15, 2019 (phase 3), participants received ophthalmic examinations and visual function assessments...This information, together with a prediction model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension. ClinicalTrials.gov Identifier: NCT00000125."

Journal • Glaucoma • Ophthalmology