Antigen presenting cells and dendritic cells; inducing immunology response
Inventors
Graddis, Thomas • Laus, Reiner • Diegel, Michael • Vidovic, Damir
Assignees
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Publication Number
US-7597894-B2
Publication Date
2009-10-06
Expiration Date
Abstract
Provided are alternative reading frame (ARF) polypeptides as well as antigen presenting cell (APC) and dendritic cell (DC) based compositions and methods that employ alternative reading frame polypeptides. ARF polypeptides and ARF polypeptide-based compositions and methods are useful in the treatment of cancer and infectious disease.
Core Innovation
The invention is directed to alternative reading frame (ARF) polypeptides and their use in cancer immunotherapy. ARF polypeptides produced by aberrant translation from tumor antigens are immunogenic and can induce CD8+ cytotoxic T lymphocyte immune responses via MHC class I presentation in vivo.
The disclosure describes ARF polypeptides derived from tumor-related antigens such as TERT and human prostatic acid phosphatase (hPAP), with ARF overlapping-sequence peptide pools encoded by portions of polynucleotides encoding the respective tumor-specific polypeptides. ARF polypeptides, fusion proteins, and vector-mediated delivery using viral vector systems are also covered.
The invention further provides antigen presenting cells, including dendritic cells, that are primed ex vivo with ARF overlapping-sequence peptide pools and then administered to stimulate an in vivo immune response. Documented immunization and tumor protection results are pool- and epitope-dependent, and a shared 11-mer epitope (RHEAAAPCQSR; SEQ ID NO: 734) is identified.
Claims Coverage
Two independent claims are identified. Each claim covers ex vivo priming of patient-derived APCs with ARF overlapping-sequence peptide pools derived from a defined tumor-specific polypeptide, followed by administration to stimulate an in vivo immune response and inhibit tumor-cell proliferation.
Ex vivo priming with TERT ARF overlapping-sequence peptide pools for APC administration
Obtaining and isolating APCs from a patient; priming the isolated APCs ex vivo with a pool of ARF overlapping-sequence peptides encoded by portions of a polynucleotide encoding the TERT tumor-specific polypeptide in reading frame 1 (rf1) or reading frame 2 (rf2) relative to the TERT rf0 AUG start site; and administering the primed APCs to the patient.
Ex vivo priming with hPAP ARF overlapping-sequence peptide pools for APC administration
Obtaining and isolating APCs from a patient; priming the isolated APCs ex vivo with a pool of ARF overlapping-sequence peptides encoded by portions of a polynucleotide encoding the hPAP tumor-specific polypeptide in reading frame 1 (rf1) or reading frame 2 (rf2) relative to the hPAP rf0 AUG start site; and administering the primed APCs to the patient.
Across both independent claims, the claim coverage centers on patient-derived APCs primed ex vivo with defined ARF overlapping-sequence peptide pools derived from tumor-specific polypeptides (TERT or hPAP), then administered to stimulate an in vivo immune response and inhibit tumor-cell proliferation.
Stated Advantages
Inhibiting proliferation of a tumor cell in a cancer patient.
Stimulating an immune response in vivo.
Documented Applications
A method for inhibiting proliferation of a tumor cell in a cancer patient having a tumor characterized by production of a TERT tumor-specific polypeptide.
A method for inhibiting proliferation of a tumor cell in a cancer patient having a tumor characterized by production of a human prostatic acid phosphatase (hPAP) tumor-specific polypeptide.
Induction of anti-tumor immune responses by administering ARF-polypeptide-pulsed dendritic cells and ARF peptide pools in mouse models, including HER-2/EL4, HER-2/B16, and mPAP/B16 challenges.
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