Peptide-based methods for treating pancreatic cancer
Inventors
Rudloff, Udo • Jaynes, Jesse M. • Lopez, Henry W. • Martin, George R. • YATES, Clayton
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Assignees
Riptide Bioscience Inc • US Department of Health and Human Services
Member
Riptide BioscienceRiptide Bioscience develops engineered peptides derived from host defense peptides found widely in nature. Their focus is on creating peptide-based therapeutics for cancer, inflammatory diseases, and microbial infections, especially those resistant to conventional treatments. The company advances both preclinical and early-stage clinical programs, collaborates with academic partners and government agencies, and holds patents for its engineered peptide design technologies.
Riptide Bioscience develops engineered peptides derived from host defense peptides found widely in nature. Their focus is on creating peptide-based therapeutics for cancer, inflammatory diseases, and microbial infections, especially those resistant to conventional treatments. The company advances both preclinical and early-stage clinical programs, collaborates with academic partners and government agencies, and holds patents for its engineered peptide design technologies.
Publication Number
US-10016480-B2
Publication Date
2018-07-10
Expiration Date
2035-10-13
Abstract
Methods for treating a subject for pancreatic cancer via administration of small anti-inflammatory peptides are disclosed. The peptides may be administered in conjunction with another therapeutic agent, such as a chemotherapeutic agent, or therapeutic regimen. In some cases, the anti-inflammatory peptide that finds use in the subject methods has the amino acid sequence Lys-Phe-Arg-Lys-Ala-Phe-Lys-Arg-Phe-Phe (SEQ ID NO:1) or a multimer, derivative, or variant thereof.
Core Innovation
The invention provides methods for treating pancreatic cancer in a subject by administering small anti-inflammatory peptides, particularly peptide A with the amino acid sequence Lys-Phe-Arg-Lys-Ala-Phe-Lys-Arg-Phe-Phe (SEQ ID NO:1) or peptide B with sequence Phe-Ala-Lys-Lys-Phe-Ala-Lys-Lys-Phe-Lys (SEQ ID NO:2), or variants thereof. These peptides exhibit strong anti-inflammatory activity in vitro and in vivo and are sufficiently stable in circulation. The methods may involve administering the peptides alone or in combination with approved chemotherapeutic agents such as gemcitabine, Abraxane, or the FOLFIRINOX regimen.
Pancreatic cancer is a malignancy with a poor prognosis, rapid spread, lack of early detection, and limited effectiveness of standard treatments including surgery, radiation, and chemotherapy. Current approved chemotherapeutic treatments improve survival by only a few months at best, partly due to characteristics like thick stromal tissue and poor drug uptake in pancreatic tumors. The peptides disclosed address the inflammatory component of pancreatic cancer and tumor drug diffusion challenges by exerting anti-inflammatory effects that reduce tumor growth and improve survival in animal models.
The invention includes pharmaceutical compositions comprising these peptides, alone or combined with other therapeutic agents, and methods for their administration via various routes including parenteral injection. The peptides were demonstrated to bind specifically to pancreatic cancer cells, influence tumor-associated macrophages to have anti-tumor activity, and improve outcomes when combined with chemotherapeutic agents. These discoveries offer new approaches for managing pancreatic cancer by targeting inflammation and tumor microenvironment components.
Claims Coverage
The patent features one independent claim defining a method of treating pancreatic cancer using specific peptides and their variants, with dependent claims adding further details and variations. There is one independent claim in total.
Use of anti-inflammatory peptides for pancreatic cancer treatment
Administering a peptide comprising the amino acid sequence Lys-Phe-Arg-Lys-Ala-Phe-Lys-Arg-Phe-Phe (SEQ ID NO:1) or a multimer, derivative, or variant thereof to a subject in need for treating pancreatic cancer.
Combination therapy with chemotherapeutic agents
The method comprising administering the peptide in conjunction with an additional therapeutic agent, particularly chemotherapeutic agents such as gemcitabine, Abraxane, FOLFIRINOX, or immune checkpoint inhibitors, to enhance treatment efficacy.
Peptide conjugation and multimer forms
Use of peptides conjugated to polyethylene glycol linkers, or as dimers or tetramers of the peptide sequence SEQ ID NO:1, to improve stability or therapeutic properties.
Administration details and dosage
Parenteral administration of the peptides at dosages from 0.05 to 25 mg/kg to human subjects for effective treatment of pancreatic cancer.
The claims collectively cover methods of treating pancreatic cancer by administering the specified peptide sequences or their variants, alone or in combination with chemotherapeutic agents, with specific embodiments relating to peptide modification, dosage, and administration routes.
Stated Advantages
Peptides have powerful anti-inflammatory activities that can reduce tumor growth and extend survival in pancreatic cancer models.
The peptides are stable in circulation, allowing pharmacokinetic and dose-response profiling for therapeutic use.
Combining the peptides with chemotherapeutic agents improves treatment efficacy compared to chemotherapy alone or other investigational agents.
Peptides show specific binding to pancreatic cancer cells and modulate the immune microenvironment favorably, including enhancing anti-tumor macrophage activity and increasing B cell presence while reducing macrophages.
Documented Applications
Treatment of pancreatic cancer in subjects, including humans, via administration of anti-inflammatory peptides (Peptide A or Peptide B) alone or in combination with chemotherapeutic agents like gemcitabine.
Combination therapy with immune checkpoint inhibitors and standard chemotherapy regimens for pancreatic cancer.
Use of the peptides in pharmaceutical compositions for parenteral administration to pancreatic cancer patients.
Use in transgenic and xenograft animal models to study anti-cancer efficacy and immune modulation in pancreatic cancer.
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