A method for preventing or for treating cancer in a mammal, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface. The method comprises creating an immune response in the mammal to at least part of the amino acid sequence of an alpha fetoprotein molecule, where the immune response comprises activating alpha fetoprotein peptide specific T lymphocytes against the cancer cells, and where the part of the alpha fetoprotein molecule is selected from the group consisting of residues 137 145 of SEQ ID NO:2, and residues 325 334 of SEQ ID NO:2 and a combination of the proceeding.

BACKGROUND

Primary liver cancer is a major cause of cancer deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, having a global incidence of approximately 1.2 million cases per year. In some areas of the world, such as Southeast Asia and Subsahara Africa, hepatocellular carcinoma is one of the most common types of malignancies. The high frequency of the disease appears to be related to the high incidence of viral hepatitis in these regions.

Curative therapy of hepatocellular carcinoma is currently limited to individuals with nonmetastatic disease and involves surgical resection of the tumor with or without liver transplantation. Even surgical resection and transplantation, however, do not cure most tumors because of recurrence after resection. Chemotherapeutic approaches to treatment have been largely ineffective.

Therefore, there remains a need for an effective treatment for hepatocellular carcinoma. The treatment should ideally be suitable for use in lesser developed countries that have the highest incidence of the disease. Further, the treatment should be appropriate for use in individuals with unresectable tumors and with metastatic disease.

SUMMARY OF THE INVENTION

In one embodiment, the present invention is a method for preventing or for treating cancer in a mammal, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface. The method comprises the step of creating an immune response in the mammal to at least part of the amino acid sequence of an alpha fetoprotein molecule where the immune response comprises activating alpha fetoprotein peptide specific T lymphocytes against the cancer cells. In one embodiment, the alpha fetoprotein peptide specific T lymphocytes are cytotoxic T lymphocytes. In a preferred embodiment, the alpha fetoprotein molecule is SEQ ID NO:2. In a particularly preferred embodiment, the alpha fetoprotein molecule is selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2, residues 325 334 of SEQ ID NO:2 and residues 542 550 of SEQ ID NO:2. In one embodiment, the cancer is hepatocellular carcinoma. In another embodiment, the mammal is a human.

In a preferred embodiment, the step of creating an immune response comprises administering to the mammal one or more than one composition including a peptide comprising at least part of the alpha fetoprotein amino acid sequence. In a particularly preferred embodiment, the peptide is selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2, residues 325 334 of SEQ ID NO:2, and residues 542 550 of SEQ ID NO:2. In another preferred embodiment, the peptide is selected from the group consisting of residues 1 9 of SEQ ID NO:2, residues 178 186 of SEQ ID NO:2, residues 218 226 of SEQ ID NO:2, residues 235 243 of SEQ ID NO:2, residues 306 315 of SEQ ID NO:2, residues 485 493 of SEQ ID NO:2, residues 492 500 of SEQ ID NO:2, residues 507 516 of SEQ ID NO:2, residues 547 556 of SEQ ID NO:2 and residues 555 563 of SEQ ID NO:2.

In another preferred embodiment, the step of creating an immune response comprises administering to the mammal one or more than one composition including dendritic cells pulsed with one or more than one peptide that forms at least part of the amino acid sequence of SEQ ID NO:2. In yet another preferred embodiment, the step of creating an immune response comprises administering to the mammal one or more than one composition including dendritic cells transduced with a recombinant adenoviral vector encoding alpha fetoprotein.

In another embodiment, the present invention is a method for preventing or for treating hepatocellular carcinoma in a human, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface, the method comprising the step of activating alpha fetoprotein cytotoxic T lymphocytes against the cancer cells to at least part of the amino acid sequence of SEQ ID NO:2 by administering to the human one or more than one composition including a peptide selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2 and residues 325 334 of SEQ ID NO:2.

In another embodiment, the present invention is a method for preventing or for treating hepatocellular carcinoma in a human, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface, the method comprising the step of activating alpha fetoprotein cytotoxic T lymphocytes against the cancer cells to at least part of the amino acid sequence of SEQ ID NO:2 by administering to the human one or more than one composition including a peptide selected from the group consisting of residues 542 550 of SEQ ID NO:2.

In another embodiment, the present invention is a method for preventing or for treating hepatocellular carcinoma in a human, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface, the method comprising the step of activating alpha fetoprotein cytotoxic T lymphocytes against the cancer cells to at least part of the amino acid sequence of SEQ ID NO:2 by administering to the human one or more than one composition including a peptide selected from the group consisting of residues 1 9 of SEQ ID NO:2, residues 178 186 of SEQ ID NO:2, residues 218 226 of SEQ ID NO:2, residues 235 243 of SEQ ID NO:2, residues 306 315 of SEQ ID NO:2, residues 485 493 of SEQ ID NO:2, residues 492 500 of SEQ ID NO:2, residues 507 516 of SEQ ID NO:2, residues 547 556 of SEQ ID NO:2 and residues 555 563 of SEQ ID NO:2.

In another embodiment, the present invention is a method for preventing or for treating hepatocellular carcinoma in a human, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface, the method comprising the step of activating alpha fetoprotein cytotoxic T lymphocytes against the cancer cells to at least part of the amino acid sequence of SEQ ID NO:2 by administering to the human one or more than one composition including dendritic cells pulsed with one or more than one peptide that forms at least part of the amino acid sequence of SEQ ID NO:2. The one or more than one peptide is selected from the dendritic cells pulsed with one or more than one peptide is selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2, residues 325 334 of SEQ ID NO:2, and residues 542 550 of SEQ ID NO:2.

In another embodiment, the present invention is a method for preventing or for treating hepatocellular carcinoma in a human, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface, the method comprising the step of activating alpha fetoprotein cytotoxic T lymphocytes against the cancer cells to at least part of the amino acid sequence of SEQ ID NO:2 by administering to the human one or more than one composition including dendritic cells transduced with a recombinant adenoviral vector encoding alpha fetoprotein.

In another embodiment, the present invention is an isolated peptide useful for preventing or for treating cancer selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2, and residues 325 334 of SEQ ID NO:2. In a preferred embodiment, the present invention is a composition for preventing or for treating cancer comprising one or more than one peptide selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2, and residues 325 334 of SEQ ID NO:2 in an amount sufficient to create an immune response to alpha fetoprotein in a mammal. The composition can additionally comprise an adjuvant. In another embodiment, the present invention is a method for preventing or for treating cancer in a human comprising the step of administering to the human one of these peptides or one of these compositions.

The present invention also includes means for preventing or for treating cancer comprising one or more than one peptide selected from the group consisting of residues 137 145 of SEQ ID NO:2, residues 158 166 of SEQ ID NO:2, residues 325 334 of SEQ ID NO:2 and residues 542 550 of SEQ ID NO:2.

In another embodiment, the present invention is an isolated peptide useful for preventing or for treating cancer having a sequence according to residues 542 550 of SEQ ID NO:2. In a preferred embodiment, the present invention is a composition for preventing or for treating cancer comprising a peptide having a sequence according to residues 542 550 of SEQ ID NO:2. The composition can additionally comprise an adjuvant. In another embodiment, the present invention is a method for preventing or for treating cancer in a human comprising the step of administering to the human this peptide or one of these compositions.

The present invention also includes means for preventing or for treating cancer comprising a peptide having a sequence according to residues 542 550 of SEQ ID NO:2.
 

Claim 1 of 2 Claims

1. An isolated peptide consisting of residues 137 145 of SEQ ID NO:2.

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