Methods and compositions for treating cancer
Inventors
Assignees
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Publication Number
US-12564623-B2
Publication Date
2026-03-03
Expiration Date
Abstract
Embodiments are directed to: (i) neutrophil secreted factors that have the capacity to kill a broad range of cancer cells without affecting the viability of non-cancer cells. Two neutrophil killing factors have been identified by the inventors: (1) eosinophil cationic protein (ECP) and (2) neutrophil elastase (ELANE); or (ii) therapeutic compositions that include CD95 degrading polypeptide components and methods of treating cancer with the same.
Core Innovation
The invention relates to killing cancer cells by CD95 degradation. It provides an anti-cancer protein therapeutic approach based on neutrophil secreted factors and CD95-degrading proteases, where CD95 (FAS/APO-1/TNFRSF6) is cleaved by a serine protease to induce cancer-specific apoptosis.
The partial content identifies eosinophil cationic protein (ECP) and neutrophil elastase (ELANE) as neutrophil factors that act in combination to kill a broad range of cancer cells. It provides mechanistic rationale including ELANE/ECP activation and ELANE-mediated CD95 cleavage through a DICE pathway (death induced by CD95R/L elimination).
The invention expands the CD95-targeting proteases to multiple serine proteases, including CTSG and PRTN3, as well as mELANE, pELA1, rELA1/RPE, and ELANE. It describes therapeutic compositions for administering these proteases to patients having cancer and includes sequence-identity and fragment criteria, including polypeptides defined by identity to SEQ ID NO: 6.
The invention further describes a method for killing a cancer cell by CD95 degradation by administering to a patient that has cancer an effective amount of a serine protease that cleaves CD95, where the cancer expresses CD95. The serine protease comprises a pancreatic porcine elastase (pELA1) polypeptide that is 96% to 100% identical to SEQ ID NO: 6, or a pELA1 polypeptide having 225 to 250 contiguous acids of pELA1 that is 98% to 100% identical to SEQ ID NO: 6.
Claims Coverage
The provided claims cover CD95-degrading serine protease administration for cancers expressing CD95, with one independent claim centered on pELA1 sequence identity criteria and dependent claims adding route and combination refinements.
Killing a cancer cell by CD95 degradation using a pELA1 serine protease
A method for killing a cancer cell by CD95 degradation comprising administering to a patient that has cancer an effective amount of a serine protease that cleaves CD95, wherein the cancer expresses CD95, and wherein the serine protease comprises a pancreatic porcine elastase (pELA1) polypeptide that is 96% to 100% identical to SEQ ID NO: 6, or a pELA1 polypeptide having 225 to 250 contiguous acids of pELA1 that is 98% to 100% identical to SEQ ID NO: 6.
Neutrophil factors and CD95-degrading proteases
Therapeutic compositions and mechanistic coverage include eosinophil cationic protein (ECP), neutrophil elastase (ELANE), CTSG, PRTN3, mELANE, pELA1, rELA1/RPE, and ELANE, with CD95 cleavage linked to cancer-cell killing.
The claims are anchored on administering a CD95-cleaving serine protease to CD95-expressing cancer, with pELA1 sequence-identity and contiguous-length limits, and broader claim language tied to CD95-degrading proteases and cancer-cell killing.
Stated Advantages
Killing a broad range of cancer cells while sparing non-cancer cells.
Mechanism-driven cancer-specific apoptosis via ELANE-mediated CD95 cleavage.
In vivo tumor-growth inhibition with immune effects.
Synergy with paclitaxel.
Documented Applications
Administering the CD95-degrading serine protease to a patient that has cancer to kill CD95-expressing cancer cells.
Intratumoral administration of the serine protease [procedural detail omitted for safety].
Combination use with a second anticancer therapy selected from chemotherapy, radiotherapy, immunotherapy, targeted therapy, or anti-hormonal therapy.
Delivery of protease to tumors using gene transfer into transgenic cells that produce exosomes or microvesicles.
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