SPANX-B polypeptides and their use
Inventors
Arya, Bira • Larionov, Vladimir L.
Assignees
US Department of Health and Human Services
Publication Number
US-9238684-B2
Publication Date
2016-01-19
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 a number of human tumors including melanoma, lung, colon, renal, ovarian, and breast carcinomas. It is demonstrated that SPANX-B acts as an immunogenic antigen recognized by human T cells, inducing both helper CD4+ and cytolytic CD8+ T cell responses. Specific SPANX-B polypeptides and polynucleotides are provided that can generate such immune responses, with potential use in treatments.
The problem addressed is the need to identify additional antigens useful as therapeutic agents to treat various cancers. Existing immunotherapy relies on cell-mediated or humoral immune responses targeting tumor-associated antigens, but lacks effective antigens for many cancer types. SPANX-B is shown to be widely expressed in human malignancies and capable of inducing relevant immune responses, making it a potent target for cancer immunotherapy.
Methods are provided for eliciting immune responses by administering therapeutically effective amounts of isolated SPANX-B polypeptides, typically of nine to twelve amino acids in length, containing sequences such as SEQ ID NO: 1, 2, 4, 26, 27, or 28. Further, methods include activating cytotoxic T cells or producing T helper cells by contacting T cells with these polypeptides. The immunodominant epitopes have been mapped, including at least one HLA-DR-restricted epitope and two HLA-A2-restricted epitopes, enabling generation of cytotoxic T cells to lyse SPANX-B-expressing tumor cells or activated helper T cells.
Claims Coverage
The patent includes one independent claim focusing on inducing CD8+ T cell immune responses using specific SPANX-B polypeptides. Two main inventive features are elaborated based on this claim.
Method for eliciting a CD8+ T cell immune response using SPANX-B polypeptide
Administering to a subject a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 4, wherein the polypeptide is nine to twelve amino acids in length, to produce a CD8+ T cell immune response.
Method for inhibiting cancer cell growth through CTL activation
Culturing cytotoxic T lymphocytes or CTL precursor cells with an isolated polypeptide comprising SEQ ID NO: 4 (nine to twelve amino acids in length) and antigen-presenting cells to produce activated CTLs that recognize cancer cells, and contacting the cancer cells with the activated CTLs to inhibit their growth.
The claims cover methods of inducing a therapeutic CD8+ T cell immune response and inhibiting cancer cell growth by using isolated SPANX-B polypeptides of specific short sequences, notably SEQ ID NO: 4, emphasizing the immunogenic capability of these polypeptides and their use in cancer immunotherapy.
Stated Advantages
SPANX-B is a potent and clinically relevant therapeutic antigen for cancer immunotherapy due to its wide expression in human malignancies and ability to induce both CD4+ helper and CD8+ cytotoxic T cell responses.
The identified immunodominant epitopes of SPANX-B enable the generation of specific T cells that can effectively recognize and kill tumor cells expressing SPANX-B.
The immunogenic SPANX-B polypeptides can activate both arms of T cell immunity, facilitating potent anti-tumor effects.
Documented Applications
Treatment of a variety of cancers including melanoma, colon carcinoma, ovarian cancer, breast cancer, myeloma, lung carcinoma, and renal cancer using immunogenic SPANX-B polypeptides to elicit immune responses.
Use of SPANX-B polypeptides for activating cytotoxic CD8+ T cells in vitro or in vivo to recognize and kill SPANX-B-expressing tumor cells.
Generation of helper CD4+ T cells to induce immune responses against tumors expressing SPANX-B.
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