About 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, 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.
*LTX-315 has not been approved by the FDA

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