A5019460893- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Nanoplatforms for cancer theranostics
- Antimicrobial Peptides and Activities
- Click Chemistry and Applications
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- Biopolymer Synthesis and Applications
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Colorectal Cancer Treatments and Studies
- Polydiacetylene-based materials and applications
- Proteoglycans and glycosaminoglycans research
- RNA modifications and cancer
- Immune Response and Inflammation
- Protein purification and stability
- Tissue Engineering and Regenerative Medicine
- Chromium effects and bioremediation
- vaccines and immunoinformatics approaches
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- CAR-T cell therapy research
Lytix Biopharma (Norway)
2014-2023
Oslo University Hospital
2017-2019
UiT The Arctic University of Norway
2010-2017
Faculty of Public Health
2014
Tromsø research foundation
2011
Oncolytic immunotherapies represent a new promising strategy in the treatment of cancer. In our efforts to develop oncolytic peptides, we identified series chemically modified 9-mer cationic peptides that were highly effective against both drug-resistant and drug-sensitive cancer cells with lower toxicity toward normal cells. Among these LTX-315 displayed superior anticancer activity was selected as lead candidate. This peptide showed relative high plasma protein binding abilities human...
Malignant melanoma is the most aggressive and deadliest form of skin cancer due to its highly metastatic potential, which calls for new improved therapies. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in species, they play a significant role first line defense against pathogens, several CAPs have shown promising potential as novel anticancer agents. Structure-activity relationship studies on CAP bovine lactoferricin allowed us de novo design short chemically...
The oncolytic peptide LTX-315, which has been de novo designed based on structure–activity relationship studies of host defense peptides, the ability to kill human cancer cells and induce specific anticancer immune response when injected locally into tumors established in immunocompetent mice. effect LTX-315 involves perturbation plasma membrane mitochondria with subsequent release danger-associated molecular pattern molecules, highlights complete regression protective responses. Treatment...
LTX-315 is a first-in-class, 9-mer membranolytic peptide that has shown potent immunomodulatory properties in preclinical models. We conducted phase I dose-escalating study of intratumoral administration patients with advanced solid tumors.Thirty-nine were enrolled, receiving injections into accessible tumors. The primary objective was to assess the safety and tolerability this approach, antitumor activity as secondary objectives. Tumor biopsies collected at baseline posttreatment for...
LTX-315 is an oncolytic peptide that elicits both local and systemic immune responses upon intratumoral injection. In the present pilot trial, we treated patients with metastatic soft tissue sarcoma combination of adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated were included trial which four proceeded to therapy. Overall, treatment was considered safe only expected manageable toxicity. The best overall clinical response stable disease...
Several cationic antimicrobial peptides demonstrate promising anticancer effects. We have recently described the properties of LTX-315, a novel synthetic peptide, against syngeneic B16 melanomas. LTX-315 induced complete regression melanomas and systemic protective immune responses following intralesional administration peptide.
Immunochemotherapy, the combined use of immunotherapy and chemotherapy, has demonstrated great promise in several cancers. LTX-315 is an oncolytic peptide with potent immunomodulatory properties designed for local treatment solid tumors. By inducing rapid immunogenic cell death through release danger-associated molecular pattern molecules (DAMPs), capable reshaping tumor microenvironment, turning "cold" tumors "hot" a significant increase tumor-infiltrating lymphocytes. We investigated...
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment LTX-315 resulted in a complete regression and systemic immune response rat fibrosarcoma model. The was T-cell dependent, also abscopal effect as demonstrated by of distal non-treated lesions. Significant infiltration CD8+ T cells observed both treated lesions, shown immunohistochemical flow cytometric analysis. rapidly killed vitro lytic mode action followed...
Abstract Cancer-associated fibroblasts (CAFs) are abundantly present in solid tumors and affect tumorigenesis therapeutic responses. In the context of clinical radiotherapy, impact irradiated CAFs to treatment outcomes is largely unexplored. Aiming at improving radiotherapy efficacy, we have here explored effect radiation on inherent pro-tumorigenic capacity animals. Ionizing was delivered cultured as single-high or fractionated doses. Tumor development compared mice receiving A549 lung...
In the present study we examined ability of amino acid derivative LTX-401 to induce cell death in cancer lines, as well capacity regression a murine melanoma model. Mode action studies vitro revealed lytic and release danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization compromised lysosomes treated cells. The use model demonstrated that majority animals with intratumoural injections showed complete long-lasting remission. Taken together, these results...
Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in broad spectrum of entities, including colorectal (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, feature particular interest non-immunogenic CRC. DTT-205 and DTT-304 were administered intratumoral injection subcutaneous tumors established from murine CRC lines CT26 MC38, complete regression was obtained the majority animals. When cured animals...
Abstract LTX-315, a novel oncolytic peptide is effective against both drug-resistant and drug-sensitive cancer cells with lower toxicity towards normal cells. Intratumoral treatment LTX-315 results in growth inhibition, complete regression long lasting tumor-specific immune responses. The effect of involves perturbation the plasma membrane distortion intracellular organelles including mitochondria subsequent release Damage-Associated Molecular Pattern molecules (DAMPs) such as ATP,...
Abstract In the present study we investigated mechanism behind killing of B16F1 murine melanoma cells by small amphipathic β(2,2)-amino acid derivative, LTX-401 (Mw<500Da). vitro, induced lytic cell death and release Danger-Associated-Molecular-Pattern Molecules(DAMPs) such as ATP HMGB-1. addition, released pro-Cathepsin-B cytochrome-c following treatment. Flow cytometry confocal microscopy studies revealed reduced signal from lysomal dye Lysotracker-DND-26, indicating loss integrity....
Abstract Host defense peptides are naturally occurring that have an important function in innate immune responses almost every life form. Recently it has been documented several host anticancer activity. Based on a peptide we do novo designed the short chemically modified LTX-315. We demonstrated LTX-315 induces immunogenic type of cell death with subsequent release danger signals (e.g. HMBG1, ATP and Cytochrome C) tumor associated antigens (TAA`s). In addition also ability to directly...
Abstract Background: Malignant melanoma is the most aggressive and deadliest form of skin cancer, with a high mortality rate among late-stage patients. This calls for new improved therapies within field. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in species, which they play significant role first line defense against pathogens, several CAPs have shown promising anticancer activity. Structure-activity relationship studies on CAP bovine lactoferricin has...
Meeting abstracts Host defense peptides are naturally occurring that have an important function in innate immune responses almost every life form. Recently it has been documented several host anticancer activity. Based on a
Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer in world and third cause of cancer-related deaths. Because HCC a relatively chemotherapy-resistant cancer, many patients are restricted to surgical resection or liver transplantation, there an urgent need develop new improved therapeutic regiments. In present study, we have investigated effect novel oncolytic compound, LTX-401, designed for local treatment solid malignancies. vitro analysis revealed that LTX-401...
Abstract The oncolytic effect of LTX-315 involves perturbation the plasma membrane and distortion mitochondrial with subsequent release DAMPs (Damage-Associated Molecular Pattern molecules) such as ATP, cytochrome C HMGB1 (1,2). Also multidomain proteins from BCL-2 family seem to be partially involved in mediated killing (3). In addition, induces hallmarks immunogenic cell death (4). Preclinical studies have demonstrated that is able induce complete tumour regression after intra-tumoral...
Abstract Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in a number of species as defense mechanism for eukaryotic cells against pathogens and an integral part the innate immune system. CAPs have broad spectrum activities including anticancer while being less cytotoxic toward non-malignant cells. The potential therapeutic application cancer has spawned interest developing oncolytic agents that display new mode action to overcome drug resistance associated with...
Abstract Background: Host defense peptides (HDPs) are naturally occurring molecules found in most eukaryotic species, where they play a significant role the first line of against pathogens. Several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on HDP bovine lactoferricin has resulted design LTX-315, short chemically modified peptide that induces immunogenic dell death. Previous animal demonstrated intratumoral (i.t.) treatment syngeneic murine...
Abstract Here, we demonstrate the potency of LTX-315 as a novel adjuvant in combination with B16F1 tumor cell lysate vaccine. is chemically modified cationic peptide derived from family molecules called host defense peptides. Through its cytolytic activity, main mechanism induction immunogenic death which leads to local inflammation by recruitment and activation immune system at injection site. This important obtain strong vaccine-specific responses. We have selected melanoma model for this...
Abstract Background: In order to develop more effective anticancer agents there is a shift from not only treating the bulk of cells in tumor but also target self renewing cancer stem (CSCs). Standard treatment with chemotherapy and radiotherapy unable eradicate CSCs therefore other modalites against are needed. LTX-315 (Oncopore®) chemically modified cytolytic peptide which equally active drug-sensitive drug-resistant cells. Earlier animal studies have demonstrated that syngenic murine A20...