LOAd700 / Lokon - LARVOL DELTA

Secondary Hemophagocytic Lymphohistiocytosis in a Young Patient With Human Immunodeficiency Virus and Epstein-Barr Virus-Associated Classic Hodgkin Lymphoma (ACG 2024) - "Labs revealed a positive HIV Ab/Ag, CD4 7 cells/mcL, viral load 700,000 copies/ml, ferritin 14,876 ng/mL, triglycerides 426 mg/dL, AST 159 unit/L, ALT 86 unit/L, total bilirubin 24 mg/dL, haptoglobin 473 mg/dL, CRP 269 mg/L, PT 29 seconds, INR 2.6, platelets 17 thou/mcL, and hemoglobin 5.9 g/dL...However, malignancies and other infectious etiologies should be ruled out prior to attributing HLH to their immunodeficiency status. Figure: Image 1: Hemophagocytosis on bone marrow aspirate."

Clinical • Anorexia • Cardiovascular • Dyslipidemia • Epstein-Barr Virus Infections • Gastroenterology • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Hodgkin Lymphoma • Human Immunodeficiency Virus • Hypertriglyceridemia • Hypotension • Immunology • Infectious Disease • Liver Failure • Lymphoma • Oncology • Rare Diseases • CD4 • HP

Induction of tumor cell apoptosis & immunogenic cell death by CD40L-armed oncolytic adenoviruses (AACR 2022) - "Here we have evaluated the anti-tumor effects of trimerized membrane-bound (TMZ)-CD40L-armed LOAd700 and TMZ-CD40L/4-1BBL-armed LOAd703 in a variety of solid tumors to understand the underlying tumor modulating mechanisms. Upregulation of cell surface calreticulin as well as the death receptors TRAIL-R1 and -R2 indicated generation of a more immunogenic phenotype of cancer cells. Thus, our findings suggest that CD40L-armed LOAd viruses could be inducers of apoptosis and immunogenic cell death in a variety of cancer types with an augmented effect in cancer cells expressing the CD40 receptor."

Immunogenic cell death • IO biomarker • Oncolytic virus • Oncology • Solid Tumor • CALR • CASP3 • CASP7 • CD40LG • HSP90AA1 • TNFRSF10A • TNFRSF10B

Improved Storage Properties and Cellular Uptake of Casticin-Loaded Nanoemulsions Stabilized by Whey Protein-Lactose Conjugate. (PubMed, Foods) - "The nanoemulsion, with an average diameter of 200 nm, possessed the capability to load 700 μg/g casticin...The main pathway for the nanoemulsion to enter HepG2 cells was pinocytosis, whereas, it entered MCF-7 predominantly through the clathrin-mediated pit. This work implies that MWPI-stabilized nanoemulsions could be utilized as an effective delivery system to load casticin and have the potential to be applied in the food and pharmaceutical industries."

Journal • Oncology

Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40. (PubMed, Cancer Gene Ther) - "Further, LOAd viruses are armed with human immunostimulatory transgenes: trimerized membrane-bound CD40L (LOAd700, LOAd703) and 4-1BBL (LOAd703). This was most prominent with LOAd703. In conclusion, LOAd viruses are of interest for MM therapy."

IO Biomarker • Journal • Oncolytic Virus

The oncolytic adenovirus, LOAd703 induces immune cell activation and controls tumor cell growth in multiple myeloma models (CRI-CIMT-EATI-AACR 2019) - "Further, LOAd viruses encodes different immunostimulatory genes, where LOAd700 encodes for trimerized membrane-bound (TMZ) CD40L and LOAd703 encodes TMZ-CD40L as well as 4-1BBL. In conclusion, LOAd infection not only upregulates markers associated with immune cell activation such as CD69 and CD107a, but also induce a more immunogenic tumor by increasing the expression levels of Fas receptor (important for triggering programmed cell death cascade) and downregulating markers associated with tumor growth and survival. Hence, LOAd viruses such as LOAd703 may be a promising therapeutic approach for treating MM."

IO Biomarker • Oncolytic Virus