Methods for modulating an immune response
Inventors
Seidel, III, Ronald D. • Chaparro, Rodolfo J.
Assignees
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Publication Number
US-11958893-B2
Publication Date
2024-04-16
Expiration Date
Abstract
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
Core Innovation
The invention concerns methods of treating cancer by administering an immune checkpoint inhibitor together with a composition comprising a protein that comprises two heterodimers. The immune checkpoint inhibitor is an antibody targeting CTLA-4, and the protein composition is administered at the same time or at different times. The approach is described as modulating an immune response for cancer treatment.
The synTac protein composition comprises two heterodimers, where each heterodimer includes a first polypeptide comprising a cancer-associated epitope other than a human papilloma virus-16 (HPV16) cancer-associated epitope, a linker set forth in specified SEQ ID NOs, and a β2-microglobulin (β2M) polypeptide. Each heterodimer also includes a second polypeptide comprising two immunomodulatory polypeptides that are variant IL-2 polypeptides, a major histocompatibility complex (MHC) class I heavy chain polypeptide, and an immunoglobulin (Ig) Fc polypeptide.
The two heterodimers are joined by one or more disulfide bonds between the Ig Fc polypeptides. The description further provides structural context for synTac polypeptides, including reduced affinity immunomodulatory domains and defined component sequences and domain/context elements, and identifies immune checkpoint inhibitor targets and example antibodies, including CTLA-4, PD-1/PD-L1, and related targets.
Claims Coverage
The consolidated claim coverage centers on one cancer-treatment method that combines a CTLA-4-targeting antibody immune checkpoint inhibitor with a synTac protein composition made of two heterodimers. It includes three inventive features.
Co-administration of CTLA-4 immune checkpoint inhibitor with synTac composition
A method of treating cancer comprising administering an immune checkpoint inhibitor that is an antibody targeting CTLA-4 and a composition comprising a protein that comprises two heterodimers, where the immune checkpoint inhibitor and the composition are administered at the same time or at different times.
Two heterodimers with cancer-associated epitope, β2M, variant IL-2, MHC class I heavy chain, and Ig Fc
A composition comprising two heterodimers in which each heterodimer comprises a first polypeptide including a cancer-associated epitope other than an HPV16 cancer-associated epitope, a linker comprising an amino acid sequence set forth in SEQ ID NOs 205-209, and a β2-microglobulin (β2M) polypeptide; and a second polypeptide including two immunomodulatory polypeptides that are variant IL-2 polypeptides comprising the amino acid sequence set forth in SEQ ID NO:49, an MHC class I heavy chain polypeptide, and an Ig Fc polypeptide.
Disulfide-bond joining of heterodimers between Ig Fc polypeptides
The two heterodimers are joined by one or more disulfide bonds between the Ig Fc polypeptides.
Overall, the claim coverage is directed to cancer treatment by co-administering a CTLA-4-targeting antibody immune checkpoint inhibitor with a synTac protein composition built from two heterodimers containing a cancer-associated epitope, β2M, variant IL-2, an MHC class I heavy chain, and an Ig Fc, with heterodimer linkage via disulfide bonds and administration at the same or different times.
Stated Advantages
Modulating an immune response for cancer treatment.
Concurrent administration with or during ongoing checkpoint inhibitor therapy.
Reduced affinity immunomodulatory domains and defined component sequences and domain/context elements.
Documented Applications
Methods of treating cancer.
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