The Wistar Institute

Daniela Santoli

Giovanni Rovera

Alessandra Cesano

TALL-104 cells, and other cytotoxic T cell lines, may be modified to increase the cytotoxicity thereof, to enhance growth properties, and/or to provide a preferred phenotype, e.g., expression of cell surface antigens, function, e.g., change in cytokine production profile, by culturing the cells in an effective amount of IL-15, optionally followed by gamma irradiation to halt proliferation.

Method of modifying cytotoxic cells and uses thereof

Methods for treating cancer in a mammalian patient having cancer and a functional immune system, and for preventing recurrences of cancer following completion of cancer therapy, are described. The methods involve administration of a course of therapy with modified TALL-104 cells, without requiring the co-administration of an immunosuppressive agent.

Method of preventing cancer recurrence

A method of treating tumors which involves a synergistic combination of chemotherapy and cell therapy is provided. The method of the invention permits reduced amounts of chemotherapeutic agents to be administered, resulting in a reduction of the side effects often associated therewith.

Method of treating malignancies

Modified TALL-104 cells to treat cancer

The invention provides a modified human cytotoxic T cell line, which is characterized by dual activity in vitro and in vivo against malignant cells and virus-infected cells. Also provided are effective and safe methods for use of the modified cells in adoptive therapy of cancer and untreatable vital diseases in MHC-mismatched recipients, and in marrow purging to achieve complete eradication of residual tumor cells from marrows of patients with leukemia and other types of cancer. Also provided are effective and safe methods for use of the cytokine stimulated, irradiated TALL-104 cells in the manufacture of a veterinary composition for adoptive therapy of canine and feline malignancies.

Modified cytotoxic tall cell line and compositions and methods for

The invention provides a modified human cytotoxic T cell line TALL-104, which is characterized by dual activity in vitro and in vivo against tumor cells and virus-infected cells. Also provided are effective and safe methods for use of the modified TALL-104 cells in adoptive therapy of cancer and untreatable viral diseases in MHC-mismatched recipients, and in marrow purging to achieve complete eradication of residual tumor cells from marrows of patients with leukemia and other types of cancer. Also provided are effective and safe methods for use of the modified TALL-104 cells in the manufacture of a veterinary composition for adoptive therapy of canine lymphoma and feline leukemias.

The invention provides cytotoxic T-ALL cell lines, and modified cytotoxic T-ALL cell lines which contain a heterologous DNA sequence. The DNA sequence may encode a product capable of stabilizing or potentiating the tumoricidal activity of the cytotoxic cell lines and a product capable of controlling the growth of the cell line. Methods for use of these cell lines are also provided.

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Bryn Mawr, PA, United States of America

Daniela Santoli