Invented by Toni Weinschenk, Oliver Schoor, Claudia Trautwein, Norbert Hilf, Steffen Walter, Harpreet Singh, Immatics Biotechnologies GmbH
The Immatics Biotechnologies GmbH invention works as followsThe invention concerns peptides, nucleic acid and cells for immunotherapeutic purposes. The present invention is particularly relevant to immunotherapy for cancer. Further, the present invention relates to tumor-associated CTL peptide epitopes. These can be used alone or in combination of other tumor-associated active pharmaceutical ingredients. The invention includes 11 novel peptide sequences, and their variants, derived from HLA class I molecules of human tumor cells. These can be used in vaccine compositions to elicit anti-tumor immunity responses.
Background for Immunotherapy for brain and neuronal tumors
Field of Invention
The invention concerns peptides, nucleic acid and cells for immunotherapeutic purposes. The present invention is particularly relevant to immunotherapy for cancer. Further, the present invention relates to tumor-associated CTL peptide epitopes. These can be used alone or in combination of other tumor-associated active pharmaceutical ingredients. The invention includes 11 novel peptide sequences, and their variants, derived from HLA class I molecules of human tumor cells. These can be used in vaccine compositions to elicit anti-tumor immunity responses.
Description of Related Art.
Gliomas are brain cancers that arise from the nervous system’s glial cells. Glial cells are also known as neuroglia or simply “glia” and they are non-neuronal cells. They provide support, nutrition, help maintain homeostasis and form myelin. Astrocytomas and Oligodendrogliomas are the two most important subgroups in gliomas. They are named after the type of normal glial cells from which they were derived (oligodendrocytes or astrocytes, respectively). Glioblastoma multiforme, which is a subgroup of astrocytomas and the most common malignant brain cancer in adults, (referred to hereinafter as glioblastoma) accounts for approximately. 40% of all malignant brain tumours are caused by glioblastoma multiforme, and approximately. CBTRUS (2006): 50% of all gliomas. It invades the central nervous systems and is the most malignant (grade IV) of all gliomas. Glioblastomas are still incurable despite steady improvements in neuroimaging and microsurgery. This brain tumor has a high lethal rate. The average life expectancy after diagnosis is between 9 and 12 months. From 1986 to 1990, the 5-year survival rate was 8.0%. The five-year survival rate after aggressive treatment including gross tumor resection has been lower than 10% to date (Burton and Praados, 2000; Nieder, 2000; Napolitano, 1999; Dazzi, 2000). There is an urgent medical need to find an effective alternative therapeutic method.
Glioblastomas tumor cells are the most undifferentiated of all brain tumors. They are high-invasive and have a high potential for migration and proliferation, which can lead to poor prognosis. Glioblastomas can cause death by infiltrative, rapid growth in the brain. These tumors are not easily resectable due to their infiltrative growth pattern. Glioblastomas can also be resistant to chemotherapy and radiation, which means that post-treatment recurrence rates for these tumors are high. The immune response to neoplastic cell is not effective in eliminating all of them after resection and radiation therapy (Roth and Weller 1999; Dix and al. 1999; Sablotzki and al. 2000).
Glioblastoma can be classified as primary glioblastoma or de novo depending on the differences in gene mechanisms during malignant transformations of undifferentiated precursor cells or astrocytes. Secondary glioblastoma can occur in younger people, up to 45 years old. Secondary glioblastoma is a form of lower-grade astrocytoma that develops over a period of 4 to 5 years. Primary glioblastoma is more common in older people with a median age of 55. Primary glioblastoma is a form of fulminant, or metastatic, glioblastoma that results in tumor progression within three months of the initial state (Pathology and Genetics of the Nervous System). 29-39 (IARC Press, Lyon, France, 2000)).
Glioblastoma spreads along myelinated nervous systems and migrates to the central nervous system. Most cases of surgery have a limited, but not permanent therapeutic effect (Neurol). Med. Chir. (Tokyo) 34, 91-94, 1994; Neurol. Med. Chir. Chir.
Malignant glioma cell production is evaded by the host’s immune systems by producing immunosuppressive drugs that impair T cells proliferation and produce the immune-stimulating cytokine IL-2. (Dix et. al., 1999).
Intracranial Neoplasms can be caused by any structure or cell type in the CNS. This includes the brain, meninges and pituitary glands, skull, embryonic tissue, and the brain. In the United States, there are 14 cases of primary brain tumors per 100,000 people. Meningiomas are the most common primary brain cancers. They account for 27% and 23% respectively. Glioblastomas make up 40% of malignant brain tumours in adults. These tumors can be aggressive and high-grade. Primary brain tumors are among the most common solid tumors in children. They are also the second leading cause of death from cancer in children after leukemia.
The search for effective treatment for glioblastomas is ongoing. These neoplastic cells can be treated with immunotherapy (or treatment via recruitment of immune system). In immuno-therapeutic trials in humans, first encouraging results were achieved. Antigen-specific CTL reactions could be inducible leading to longer median survival times than standard treatment with minimal toxicities (Heimberger and al., 2006).
There is a need for an effective and safe treatment option for brain cancers. This can be done without the use of chemotherapeutics or other drugs that could cause severe side effects. This invention fulfills that need.
The present invention provides peptides that are selected from the SEQID NO:1 to 11 group or a variant thereof which has 80% homologity to SEQID NO:11 or a variant which induces T cells to cross-react with the peptide. The peptide should be able to bind to either a class I or II of the human major hertocompatibility complicated (MHC). It should also be capable of stimulating CD4 and CD8 T cells. Other embodiments are at least 80% identical to the sequence in SEQ DNO:1 to 11 and can bind to either a class I or II of the human major mytocompatibility complexity (MHC).
A preferred embodiment of the peptide includes the amino acid sequence described in SEQ ID No:1. This invention also includes a variant of the peptide that binds to the MHC class I molecule HLA-A*0205 allele. The variant can stimulate CD8 cells and has the following motif: X1, X2, and X3, X4, and X5, and X6, and X7, and X8, and X9, respectively.
X1 is A; V or Y;
X2 is L
X3 is P, F, I, or M;
X4″ is T, E or D, K, and N.
X5 is L. V. L. or I;
X6 is M. I, V. L. I or A;
X7 is H; or V;
X8 is Q, Y, andClick here to view the patent on Google Patents.