Også LTX nevnt som "LTX-315, one of the most promising and extensively studied oncolytic peptides"

Oncolytic peptides are highly effective on remodeling the tumor microenvironment and potentiating the anticancer immunity through multiple mechanisms, particularly by inducing immunogenic cell death. Intriguingly, a recent study demonstrates that LTX-315, one of the most promising and extensively studied oncolytic peptides, inhibits PD-L1 expression via ATP11B, thus enhancing the effectiveness of cancer immunotherapy by targeting the PD-1/PD-L1 axis. Therefore, this commentary discusses the broad effects and perspectives of oncolytic peptides on anticancer immunity, further highlighting the potential issues and directions of oncolytic peptides in cancer immunotherapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295653/

Abstract desember-2022

Interventional Oncolytic Immunotherapy with LTX-315 for Residual Tumor after Incomplete Radiofrequency Ablation of Liver Cancer

Radiofrequency ablation (RFA) is a favorite treatment approach for patients with liver cancer, one of the most common malignancies worldwide. However, incomplete RFA often occurs in irregular and medium-to-larger (>3 cm) hepatic tumors. The aim of this study was to validate the feasibility of interventional oncolytic immunotherapy with LTX-315 for residual tumors after incomplete RFA of liver cancers. LTX-315, injected into tumor margins through the electrode prongs during the ablation procedure, can directly kill tumor cells and activate an anti-tumor immune response. This treatment strategy facilitated the creation of a clear ablated tumor margin. The evidence of this study may open up new avenues to prevent residual tumors after RFA of irregular and medium-to-large liver cancers.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777024/

Abstract: 07.12.2023

LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients with metastatic soft tissue sarcoma

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 with the combination of LTX-315 and adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated patients were included in the trial and treated with LTX-315 of which four patients proceeded to adoptive T-cell therapy. Overall, the treatment was considered safe with only expected and manageable toxicity. The best overall clinical response was stable disease for 208 days, and in this patient, we detected tumor-reactive T cells in the blood that lasted until disease progression. In three patients T-cell reactivity against in silico predicted neoantigens was demonstrated. Additionally, de novo T-cell clones were generated and expanded in the blood following LTX-315 injections. In conclusion, this pilot study provides proof that it is feasible to combine LTX-315 and adoptive T-cell therapy, and that this treatment can induce systemic immune responses that resulted in stabilization of the disease in sarcoma patients with otherwise progressive disease. Further optimization of the treatment protocol is warranted to increase clinical activity. ClinicalTrials.gov Identifier: NCT03725605


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732595/

StockWizard, legger du inn ticker?
Synd at Lytix har blitt uforskyldt rammet av ULTI fiaskoen, og synd for både aksjonærer og ansatte i selskapet, samt kreftpasienter at ULTI sin teknologi ikke ser ut til å fungere særlig optimalt.
Lytix har som du lister opp i starttråden en helt annen innfallsmetode mhp. kreftbehandling, hvor stimulering av kroppens eget forsvarsverk, T- cellene er det essensielle. Lytix sin teknologi skal også kunne behandle nye muterte kreftceller, noe som er særdeles viktig for å kunne ta knekken på kreftsvulsten.

Fant også mye nyttig på Verrica sin side om LTX-315:
LTX-315 Mechanism of Action
Lactoferrin-derived lytic peptide LTX-315. NCI Drug Dictionary 2020.
A peptide derived from human lactoferrin, with potential lytic and immunostimulating activities.
LTX-315 may bind to the tumor cell membranes and subsequently lyse tumor cells, thereby inducing tumor cell necrosis. In turn, presentation of the tumor antigens to the immune system may induce systemic innate and adaptive immune responses mediated by anti-tumor natural killer (NK) cells, cytotoxic T lymphocytes, and natural killer T (NKT) cells. This may trigger an immune response against tumor associated antigens on tumors distant from the primary tumor.
https://www.cancer.gov/publications/dictionaries/cancer-drug/def/lactoferrin-derived-lytic-peptide-ltx-315
LTX-315: A first-in-class oncolytic peptide that reshapes the tumor microenvironment. Lytix Biopharma 2017.
LTX-315 induces a unique type of immunogenic cell death
LTX-315 treatment leads to increased tumor infiltration of CD8+ T cells
LTX-315 demonstrates synergy with other standard of care cancer therapies
LTX-315 increases the number and diversity of T cell clones
http://www.lytixbiopharma.com/uploads/posters/SITC%202017_LTX-315_A%20first-in-class%20oncolytic%20peptide%20that%20reshapes%20the%20tumor%20microenvironment.pdf
LTX-315, CAPtivating Immunity with Necrosis. Sistigu A, Manic G, Vitale I. Cell Cycle. 2016; 15(9): 1176–1177.
LTX-315 is a helical CAP [Cationinc Antimicrobial Peptide] optimized for membrane destabilization, which has been recently shown to induce cell lysis when administered intralesionally
This [leads] to the release of immunomediators into the tumor microenvironment and unleashed an inflammatory response whereby specific cytotoxic T cells eradicated residual cancer cells.
LTX-315 epitomizes an oncolytic agent that, due to its immunogenic potential, may represent a new cancer immunotherapeutic approach for triggering tumoricidal immune responses at will
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889301/
LTX-315 Basic/Background Research
LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects. Liao HW, Garris C, Pfirschke C, et al. Cell Stress. 2019; 3(11): 348–360.

LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in Phase II clinical trials.
Here [the study] aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. [The study reports] LTX-315 mediates profound antitumor effects against Braf-and Pten-driven melanoma and delays the progression of Kras- and P53-driven soft tissue sarcoma in mice.
Additionally, [the study shows] in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of lymphocytes. The second phase of response, which continues over weeks, is defined by long-term alteration of the tumor microenvironment; the changes induced by LTX-315 are most notably characterized by CD8+ T cell infiltration. [The study further shows] that these CD8+ T cells are involved in suppressing melanoma outgrowth in mice and report similar CD8+ T cell infiltration following LTX-315 treatment in melanoma and sarcoma patients.
Taken together, these findings reveal LTX-315’s multiple antitumor effects, including disrupting the tumor vasculature and promoting the conversion of poorly immunogenic tumors into ones that display antitumor T cell immunity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859426/
Cell cycle progression data on human skin cancer cells with anticancer synthetic peptide LTX-315 treatment. Santa-Gonzalez GA, Patino-Gonzalez E, Manrique-Moreno M. Data in Brief. 2020; 20: 105443.
Skin cancer, including melanoma and non-melanoma (NMSC), represents the most common type of malignancy in the white population. The incidence rate of melanoma is increasing worldwide, while the associated mortality remains stable. On the other hand, the incidence of NMSC varies widely.
Camilio and collaborators recently described the anticancer properties of LTX-315, a novel synthetic anticancer peptide, commercialized as Oncopore™. Despite various studies demonstrating the efficiency of LTX-315 therapy in inducing cancer cell death, the effects on cell cycle progression of this antitumoral peptide are poorly understood.
In this research, [the study presents] data about the effect of LTX-315 on the cell cycle of two skin cancer cell lines: epidermoid carcinoma cells (A431) and melanoma cells (A375); as well as on an immortalized normal keratinocyte cell line, HaCaT. Additionally, its cytotoxicity on the cells was determined by measuring the uptake of propidium iodide, in order to establish its relationship with cell cycle progression. The analysed data obtained by flow cytometry show different cell cycle distributions in non-tumoral and skin cancer-derived cell lines in response to LTX-315 treatment. Non-tumoral cells showed a sub-G1 peak, while for tumoral cells there was a shift in the G1peak without producing an obvious distant and distinct sub-G1 peak. This data is in accordance with a major decrease in cell viability in non-cancer cells.
https://www.sciencedirect.com/science/article/pii/S2352340920303371
LTX-315 Clinical Data
LTX-315 Clinical Trials. Clinicaltrials.gov 2020.
List of Ongoing and Completed Clinical Trials Registered with ClinicalTrials.gov.
https://clinicaltrials.gov/ct2/results?cond=&term=ltx315&cntry=&state=&city=&dist=
https://verrica.com/key_publications/about-ltx-315/

Lytix Biopharma-sjefen ser lyse tider for selskapets utprøvende kreftmedisiner
Fremskritt i egne kliniske studier og for lisensieringspartner Verrica Pharmaceuticals med LTX-315. Ny legemiddelkandidat er snart klar for kliniske studier. Øystein Rekdal har gode og travle dager på jobb som direktør i det norske biotekselskapet Lytix Biopharma.

https://www.healthtalk.no/kreft/lytix-biopharma-sjefen-ser-lyse-tider-for-selskapets-utprovende-kreftmedisiner/169567?noLog=1