Methods for modulating an immune response
Inventors
Seidel, III, Ronald D. • Chaparro, Rodolfo J.
Assignees
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Publication Number
US-11993641-B2
Publication Date
2024-05-28
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 relates to treating an individual having a cancer that expresses a human papilloma virus-16 (HPV16) E7 antigen by administering a combination of an immune checkpoint inhibitor that is an anti-PD-1 antibody and a protein that is a homodimer of two multimeric polypeptides. The immune checkpoint inhibitor and the protein are administered at the same time or at different times.
Each multimeric polypeptide comprises a first polypeptide including a peptide comprising an HPV16 E7 epitope and a β2-microglobulin (β2M) polypeptide, and a second polypeptide including first and second variant IL-2 polypeptides, a major histocompatibility complex (MHC) class I heavy chain polypeptide, and an immunoglobulin (Ig) Fc polypeptide.
The two multimeric polypeptides are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one multimeric polypeptide to the Ig Fc polypeptide of the other multimeric polypeptide. The disclosure further frames a treatment rationale involving modulation of immune responses with synTac (T-cell modulatory multimeric polypeptide) together with an immune checkpoint inhibitor.
Claims Coverage
The independent claim coverage centers on a combination treatment for cancer expressing an HPV16 E7 antigen using an anti-PD-1 immune checkpoint inhibitor together with a homodimeric protein formed by two multimeric polypeptides. Four inventive features are identified.
Combination therapy with anti-PD-1 immune checkpoint inhibitor and homodimeric synTac protein
A method of treating an individual having a cancer that expresses an HPV16 E7 antigen by administering a combination of an immune checkpoint inhibitor that is an anti-PD-1 antibody and a protein that is a homodimer of two multimeric polypeptides, with the immune checkpoint inhibitor and the protein administered at the same time or at different times.
HPV16 E7 epitope with β2-microglobulin in first polypeptide
Each multimeric polypeptide comprises a first polypeptide including a peptide comprising an HPV16 E7 epitope and a β2-microglobulin (β2M) polypeptide.
Variant IL-2, MHC class I heavy chain, and Ig Fc in second polypeptide
Each multimeric polypeptide comprises a second polypeptide including first and second variant IL-2 polypeptides, a MHC class I heavy chain polypeptide, and an immunoglobulin (Ig) Fc polypeptide.
Disulfide-bonded homodimer joining Ig Fc between multimeric polypeptides
The two multimeric polypeptides are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one multimeric polypeptide to the Ig Fc polypeptide of the other multimeric polypeptide.
The independent claim coverage centers on combination treatment of cancer expressing an HPV16 E7 antigen using an anti-PD-1 antibody together with a homodimeric protein built from two multimeric polypeptides. Each multimeric polypeptide includes an HPV16 E7 epitope with β2M, and a second polypeptide that contains variant IL-2 polypeptides together with an MHC class I heavy chain and an Ig Fc, with the two multimeric polypeptides connected via disulfide bonds between their Ig Fc domains.
Stated Advantages
Potential synergy that may allow reduced dosing and toxicity while improving clinical outcomes.
Improved clinical outcomes, including tumor reduction and survival.
Documented Applications
Treating an individual having cancer that expresses a human papilloma virus-16 (HPV16) E7 antigen using an anti-PD-1 immune checkpoint inhibitor in combination with a homodimeric T-cell modulatory multimeric polypeptide (synTac) administered at the same time or at different times.
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