Variant survivin vaccine for treatment of myeloma
Inventors
LOCKE, FREDERICK L. • Altieri, Dario • Antonia, Scott • Anasetti, Claudio • Gabrilovich, Dmitry
Assignees
H Lee Moffitt Cancer Center and Research Institute Inc • Wistar Institute of Anatomy and Biology
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12344642-B2
Publication Date
2025-07-01
Expiration Date
Abstract
The invention concerns a variant (double mutant form) of the survivin polypeptide; nucleic acid molecules encoding the survivin variant; antigen presenting cells (APCs) such as dendritic cells, or APC precursors, comprising the variant survivin polypeptide or encoding nucleic acid sequence; and methods for treating a malignancy, such as myeloma, or for inducing an immune response, utilizing a variant survivin polypeptide, nucleic acid molecule, or APC.
Core Innovation
The invention provides an antigen presenting cell comprising a variant survivin polypeptide, or a nucleic acid sequence encoding the variant survivin polypeptide, wherein the variant comprises at least consecutive amino acids 16-87 of the human wild-type survivin polypeptide SEQ ID NO:1 in the N-terminal zinc-binding baculovirus inhibitor of apoptosis protein repeat (BIR) domain. The variant survivin polypeptide is a subsequence of the human wild-type survivin polypeptide and contains alanine substitutions at position 34 and position 84 relative to the human wild-type survivin polypeptide.
The invention further relates to compositions comprising the variant survivin polypeptide, or a nucleic acid encoding it, an antigen presenting cell, and an adjuvant, as well as compositions that include a pharmaceutically acceptable carrier. The disclosed framework centers on survivin-targeting dendritic cell adenovirus settings for multiple myeloma and immunologic evaluation intended to assess T-cell immunomodulatory phenotypes and survivin-reactive responses.
The described approach includes treating a malignancy that is myeloma by administering an effective amount of a variant survivin polypeptide or an expression construct encoding the variant, together with an antigen presenting cell comprising the variant survivin polypeptide or its nucleic acid. The framework also includes monitoring for safety and toxicity, with attention to hematopoietic engraftment, neutrophil repopulation after autologous transplant, and autoimmune risk in survivin-expressing tissues.
Claims Coverage
The document identifies three independent claims directed to an antigen presenting cell, a composition, and a method. Across these claims, the inventive scope is anchored by a specific survivin variant polypeptide definition and its use with antigen presenting cells, adjuvant, or treatment of myeloma.
Variant survivin subsequence with alanine at positions 34 and 84
An antigen presenting cell comprising a variant survivin polypeptide, or a nucleic acid sequence encoding the variant survivin polypeptide, wherein the variant comprises at least consecutive amino acids 16-87 of the human wild-type survivin polypeptide SEQ ID NO:1 in the N-terminal zinc-binding baculovirus inhibitor of apoptosis protein repeat (BIR) domain, modified to have alanine at position 34 and alanine at position 84, and wherein the variant survivin polypeptide is a subsequence of the human wild-type survivin polypeptide.
Vaccine or therapeutic composition with antigen presenting cell and adjuvant
A composition comprising the variant survivin polypeptide, or a nucleic acid sequence encoding the variant survivin polypeptide, an antigen presenting cell, and an adjuvant, with the same survivin variant definition as the antigen presenting cell claim.
Treating myeloma with variant survivin and antigen presenting cells
A method for treating a malignancy, wherein the malignancy is myeloma, by administering an effective amount of the variant survivin polypeptide or an expression construct encoding the variant, together with an antigen presenting cell comprising the variant survivin polypeptide or the nucleic acid encoding it.
The inventive features consistently center on the defined survivin variant subsequence with alanine substitutions at positions 34 and 84, and its incorporation into an antigen presenting cell, a composition with adjuvant, and a method for treating myeloma.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Variant survivin vaccine therapy for myeloma, including treatment of a malignancy where the malignancy is myeloma.
Induction or expansion of survivin reactive CD4+ T cell responses, including survivin-reactive CD4+CD25− T cells, in healthy donors and myeloma patients.
Optional hematopoietic cell transplantation, including autologous hematopoietic cell transplantation or stem cell transplantation, in combination with the described variant survivin treatment.
Co-immunization with Prevnar 13 (PCV-13) / CRM197 adjuvant in the context of the variant survivin therapy.
Interested in licensing this patent?