LY458202 / Eli Lilly - LARVOL DELTA

Supramolecular STING-Hydrogel Spatiotemporally Boosts Tumor-Derived Extracellular Vesicle-Based Personalized Vaccine for Enhanced Cancer Immunotherapy. (PubMed, Adv Mater) - "We demonstrate that this vaccine promotes dendritic cells (DCs) recruitment and establishes an immune-permissive niche through spatiotemporal control over antigen-adjuvant distribution and prolonged APC-antigen engagement...In a postoperative breast cancer model, patient-tailored TEV vaccines also markedly prevent tumor recurrence and metastasis. This readily customizable platform represents a robust and translatable strategy for personalized cancer immunotherapy."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor • STING

A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering. (PubMed, PLoS Comput Biol) - "Increasing RyR density prolonged APCL in the basal state but shortened APCL during βAR stimulation...When realistic higher RyR density and superclustering were added to the model, APCL further shortened to 231.9 ms. Thus, dynamic nanoscale changes in RyR network provide a new powerful pacemaker mechanism."

Journal

Engineered Nanobodies for Durable Tolerance in Allergic Asthma (IMMUNOLOGY 2026) - "Thus, there is unmet need for transformative therapies that induce durable, antigen-specific tolerance in asthma. Our nanobody-engineering approach co-delivers the allergen and glucocorticoids (dexamethasone) to all antigen-presenting cells (APCs) by targeting major histocompatibility complex class II (MHCII)...We have analyzed systemic and intranasal delivery by positron emission tomography and probed the engaged APC subsets by multiparametric cytofluorometry... Allergic asthma is a common disorder affecting >150 million people worldwide, though no curative treatment is available. We established a potent approach to intercept allergic airway inflammation in an ovalbumin mouse model. We will now analyze B cell and other APC subsets by single cell RNA sequencing to delineate the molecular mechanisms of tolerance induction."

Asthma • Immunology • Inflammation • Respiratory Diseases • HLA-DRB1

Slm1, an F-BAR and PH domain-containing protein, regulates heat-induced turnover of nutrient transporter to control plasma-membrane quality. (PubMed, FEBS J) - "To address this question, we engineered a Tet-off strain that enables controlled expression of GFP-tagged Slm1 (GFP-Slm1) and found that Slm1 is massively overexpressed (~ 48-fold) in the absence of doxycycline. Under heat stress, excess Slm1 selectively delays the endocytic turnover and vacuolar degradation of heat-damaged APC transporters, leading to their prolonged accumulation at the PM. Together, our findings identify Slm1 as a regulator of PMQC that modulates the heat-induced turnover of nutrient transporters and other PM proteins and reveal that eisosome function buffers against Slm1-driven defects in actin-dependent membrane trafficking."

Journal • Targeted Protein Degradation

Exosomes from APCs ameliorate human skin fibroblast senescence via p53/p21 signaling pathway. (PubMed, Tissue Cell) - "The proliferation capacity of aged APCs was significantly reduced...Notably, yAPC-Exos exerted more pronounced anti-senescent effects than oAPC-Exos. Taken together, yAPC-Exos may represent an effective therapeutic strategy for aging-related skin pathologies and cosmetic applications."

Journal • Dermatopathology • CDKN1A • SIRT1

Quercetin rejuvenates aged adipose progenitor cells by attenuating inflammatory pathways. (PubMed, Exp Gerontol) - "Strikingly, while quercetin exerted concentration-dependent effects on the vitality and function of APCs, only moderate doses specifically restored the adipogenic differentiation of aged APCs. Mechanistically, this rejuvenating effect was primarily mediated through the suppression of pro-inflammatory pathways. Together, our findings provide novel mechanistic insights into APCs aging in iWAT and identify quercetin as a promising rejuvenative agent for the treatment of adipose tissue dysfunction and related metabolic disorders in aging."

Journal • Inflammation • Metabolic Disorders

Collateral Damage: Hemoptysis in a Child With Fontan Physiology (ATS 2025) - "CT angiography was repeated which again revealed GGOs and numerous enlarged APCs; some of these vessels were present beside the right mainstem bronchus and its lower branches formed by a hypertrophied bronchial artery along with intercostal and phrenic arteries...Embolizing too many APCs could significantly reduce pulmonary blood flow and promote APC formation and further bleeding. Bronchoscopy with BAL in a non-critically ill child is a safe procedure that can optimize localization and prevention of embolizing incorrect areas."

Clinical • Cardiovascular • CNS Disorders • Cough • Fibrosis • Hematological Disorders • Immunology • Infectious Disease • Movement Disorders • Pain • Parkinson's Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

High-throughput discovery of MHC class I- and II-restricted T cell epitopes using synthetic cellular circuits. (PubMed, Nat Biotechnol) - "Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context...We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity."

Journal • Cardiovascular • Infectious Disease • Melanoma • Oncology • Solid Tumor • Testicular Cancer

Aging is associated with accumulated T follicular helper cells with decreased metabolic function (P1046) (IMMUNOLOGY 2023) - "We hypothesize that age-associated Tfh accumulation may impair antigen-specific Tfh induction and subsequent germinal center responses. Current studies use live-cell 2-photon microscopy to track the impact of age on lymphocyte motility and Tfh:B interactions, in order to determine the relative contributions of aged APCs, non-specific aged Tfh, and aged regulatory T cells to germinal center deficiency."

Infectious Disease • CD4

A joinpoint and age-period-cohort analysis of ocular cancer secular trends in Iran from 2004 to 2016. (PubMed, Sci Rep) - "ASIR of retinoblastoma was significantly increased (averaged APC = 20.7, 9-33.7) between 2004 and 2016...Excepting retinoblastoma, all ocular cancer incidence trends were downward over a 13-year period; however, it was increasing between 2004 and 2009 cancer. ASIR was significant aging in Iran."

Journal • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor

Zinc finger protein 277 is an intestinal transit-amplifying cell marker and colon cancer oncogene. (PubMed, JCI Insight) - "Zfp277 deficiency attenuated intestinal epithelial cell proliferation and tumor formation, and strikingly prolonged ApcMin/+ mouse survival...In both human colon cancer cells and the murine colon, ZNF/Zfp277 deficiency induced p21WAF1 expression and promoted senescence. Our findings identify ZNF/Zfp277 as both a TAC marker and colon cancer oncogene that regulates cellular proliferation and senescence, in part by repressing p21WAF1 expression."

Journal • Colon Cancer • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Oncology • Solid Tumor • CDKN1A

[VIRTUAL] REAL WORLD EXPERIENCE OF PORCINE FVIII USE IN COMPLEX PELVIC SURGERY AND ACQUIRED HAEMOPHILIA A: CASE REPORT AND MULTI‐DISCIPLINARY TEAM REFLECTION. (EAHAD 2021) - "Introduction: Porcine recombinant factor VIII, Obizur® (pFVIII) was recently commissioned by NHS England for bleed management in acquired haemophilia A (AHA) if undetectable or low titre ( 200iU/dL with 1 mg/kg prednisolone pre-operatively...Concern remained of thrombosis risk with prolonged aPCC dosing and immobility post pelvic surgery...The daily UK cost of steady state pFVIII dosing (2000u TDS) maintaining FVIII:C troughs > 70iU/dL was 92% of the cost of 50u/kg QDS FEIBA... pFVIII provided a 4 week therapeutic window in this complex surgical case. Our multi-disciplinary team reflections on using pFVIII for the first time are of simplicity of use and security of monitoring and efficacy. These are valuable attributes over the established bypass agents in such a clinical scenario."

Real-World Evidence • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Hemophilia • Immunology • Infectious Disease • Oncology • Ovarian Cancer • Rare Diseases • Septic Shock • Solid Tumor • Thrombosis

Gastric precancerous lesions present in Apc mice. (PubMed, Biomed Pharmacother) - "The Apc mouse is an animal model for familial adenomatous polyposis, and aged Apc mice also spontaneously develop multiple tumors in their stomachs...The effect of mutations in the Apc gene on chronic gastritis and gastric precancerous lesions was characterized in Apc mice. These results suggest that Apc mice represent a genetic model for mechanistic studies and drug discovery in gastric precancerous lesions."

Journal • Preclinical • Gastric Cancer • Immunology • Oncology

Impact of aortopulmonary collateral flow and single ventricle morphology on longitudinal hemodynamics in Fontan patients: A serial CMR study. (PubMed, Int J Cardiol) - "Longitudinal CMR data in a cohort of clinically stable Fontan patients revealed no significant changes in SV dimensions and myocardial performance while APC flow decreased spontaneously. Patients with a systemic RV seem to be at risk for permanent SV volume overload through APCs and might therefore benefit from consequent interventional APC embolization."

Clinical • Journal

APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression. (PubMed, BMC Cancer) - "Our work adds APC2 to the growing list of WNT-signalling members that regulate ovarian homeostasis, fertility and suppress GCT formation. Importantly, given that the APC2-deficient mouse develops tumours that recapitulate the molecular signature and histological features of human adult GCTs, this mouse has excellent potential as a pre-clinical model to study ovarian subfertility and transitioning to GCT, tumour biology and for therapeutic testing."

Journal