Methods and compositions related to therapeutic peptides for cancer therapy
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Publication Number
US-12611443-B2
Publication Date
2026-04-28
Expiration Date
Abstract
Embodiments of the current invention provide a solution to the problems associated with balancing patient toxicity with broad efficacy of cancer therapy. In particular, embodiments are directed to anti-cancer peptides that demonstrate a broad anti-cancer efficacy with a limited toxicity to normal or non-cancer cells.
Core Innovation
The invention concerns therapeutic anti-cancer peptides derived from ELANE-mediated cleavage of human CD95 (Fas/Apo-1). The peptides are selected to contain ELANE cleavage sites, including peptides corresponding to ELANE cleavage site 1 and cleavage site 2, with emphasis on C-terminal fragments containing a DD-containing sequence context (SEQ ID NO:2/3/4/5).
The disclosed approach is based on the ELANE release of CD95 death-domain (DD) fragments, and the resulting selective killing of cancer cells with limited toxicity to non-cancer cells. The mechanism is described as mimicking CD95 knockdown killing programs and as inducing apoptosis through DNA damage, mitochondrial ROS, and caspase activation.
The disclosure provides mechanistic support for the CD95 cleavage sites, including site 1 and site 2, and includes evidence for downstream apoptotic markers such as cleaved PARP and cleaved caspase-3, as well as b3H2AX and mitochondrial ROS. The document also reports attenuation of tumor growth with ELANE and includes immune-related findings involving dendritic cells and CD8+ T cells, including CD8-dependent abscopal effects.
In addition, the disclosure describes embodiments for administration and peptide composition, including injection and peptide sequence identities/variants and related composition forms. It also describes delivery vehicle embodiments such as liposome/nanoparticle delivery vehicle and related expression vector/expression cassette concepts, including a doxycycline-inducible Tet-on system.
Claims Coverage
1 independent claim is explicitly provided (clm-00001). It recites a method comprising an inventive combination of an anti-cancer therapeutic composition with specific ELANE-derived peptide selections, a defined cancer type scope, and administration by injection.
Administering a therapeutic peptide selected from SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5
The method administers an effective amount of a therapeutic composition comprising a peptide selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5 to a subject having cancer.
Treating breast cancer, melanoma or lung cancer by injection
The subject having cancer is limited to breast cancer, melanoma or lung cancer, and the therapeutic composition is administered by injection.
The independent claim is directed to treating cancer by injecting a therapeutic composition containing an effective amount of an ELANE-derived peptide selected from SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5, for breast cancer, melanoma, or lung cancer.
Stated Advantages
Selective killing of cancer cells with limited toxicity to non-cancer cells.
Induction of apoptosis via DNA damage, mitochondrial ROS, and caspase activation.
Attenuation of tumor growth.
Immune effects involving dendritic cells and CD8+ T cells, including CD8-dependent abscopal effects.
Documented Applications
Treating cancer in a subject having breast cancer, melanoma or lung cancer using a therapeutic composition administered by injection.
Immune-mediated anti-tumor effects described as involving DCs and CD8+ T cells, including CD8-dependent abscopal effects.
In vitro and in vivo tumor growth attenuation with intratumoral ELANE.
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