SPANX-B polypeptides and their use
Inventors
Arya, Bira • Larionov, Vladimir L.
Assignees
US Department of Health and Human Services
Publication Number
US-8664183-B2
Publication Date
2014-03-04
Expiration Date
2030-02-26
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Abstract
It is disclosed herein that SPANX-B is uniquely expressed in a number of human tumors and that SPANX-B is an immunogenic antigen that is recognized by human T cells inducing helper CD4+ and cytolytic CD8+ T cell responses. Specific SPANX-B polypeptides and polynucleotides are disclosed that can be used to generate an immune response. In several embodiments, these polypeptides can be used for the treatment of a variety of cancers, including melanoma, colon carcinoma, ovarian cancer, breast cancer, myeloma, lung carcinoma and renal cancer.
Core Innovation
The invention discloses that SPANX-B is uniquely expressed in various human tumors including melanoma, colon carcinoma, ovarian cancer, breast cancer, myeloma, lung carcinoma, and renal cancer. SPANX-B is an immunogenic antigen recognized by human T cells, inducing helper CD4+ and cytolytic CD8+ T cell responses. Specific SPANX-B polypeptides and polynucleotides are disclosed for generating such immune responses, which can be therapeutically used for the treatment of these cancers.
The problem addressed is the need to identify additional tumor antigens that can be used as therapeutic agents to treat different types of cancer. Existing immunotherapies have limitations, and improved strategies are needed to evoke effective immune responses specifically targeting tumor-associated antigens for various malignancies.
The disclosure demonstrates that SPANX-B is widely expressed in human malignancies and its expression correlates with advanced and metastatic disease in melanoma. Human T cells from peripheral blood that recognize SPANX-B can be expanded to produce SPANX-B-specific CD4+ helper and cytolytic CD8+ T cells. Immunodominant epitopes within SPANX-B have been mapped, providing peptides that generate cytotoxic T cells capable of specifically lysing tumor cells expressing SPANX-B or producing activated helper T cells.
Claims Coverage
The claims include one independent method claim for eliciting a CD8+ T cell immune response and one independent composition claim for an isolated polypeptide.
Method for eliciting a CD8+ T cell immune response against a tumor
Administering a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 2, nine to twelve amino acids in length, thereby producing CD8+ T cell immune response against the tumor.
Isolated immunogenic polypeptide
An isolated polypeptide comprising the amino acid sequence SEQ ID NO: 2, nine to twelve amino acids in length, or consisting of SEQ ID NO: 2.
Nucleic acid encoding the polypeptide and expression vectors
An isolated polynucleotide encoding the polypeptide comprising SEQ ID NO: 2, operably linked to a promoter, and vectors comprising such polynucleotides.
Host cell transformed with vector
An isolated host cell transformed with the recombinant vector that includes the polynucleotide encoding the SEQ ID NO: 2 polypeptide.
Method for inhibiting the growth of a cancer cell using activated CTLs
Culturing cytotoxic T lymphocytes (CTLs) or CTL precursor cells with the SEQ ID NO: 2 polypeptide and antigen-presenting cells to produce activated CTLs that recognize the cancer cell, and contacting the cancer cell with these activated CTLs to inhibit its growth.
The claims focus on using specific SPANX-B-derived immunogenic polypeptides, particularly the sequence of SEQ ID NO: 2, and related nucleic acids and vectors, to induce CD8+ T cell immune responses for treating various cancers, as well as compositions and methods for activating CTLs to inhibit cancer cell growth.
Stated Advantages
SPANX-B is a potent and clinically relevant therapeutic antigen widely expressed in human malignancies, particularly associated with advanced and metastatic melanoma.
The identified SPANX-B peptides can activate both CD4+ helper and CD8+ cytotoxic T cells, enabling a robust cell-mediated immune response against tumors.
The immunogenic peptides are capable of inducing cytotoxic T cells that specifically lyse tumor cells expressing SPANX-B, implying effectiveness in cancer immunotherapy.
Documented Applications
Use of SPANX-B polypeptides to generate immune responses for the treatment of cancers including melanoma, lung carcinoma, colon carcinoma, renal carcinoma, ovarian carcinoma, breast carcinoma, and myeloma.
Administration of isolated immunogenic SPANX-B polypeptides to elicit CD4+ and CD8+ T cell responses in subjects with tumors expressing SPANX-B.
In vitro stimulation of T cells with SPANX-B peptides or protein to generate activated cytotoxic T lymphocytes or helper T cells for therapeutic applications.
Use of recombinant viral vectors or nucleic acids encoding SPANX-B polypeptides for vaccination or immunotherapy against SPANX-B-expressing tumors.
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