University of Minnesota

The United States of America As Represented by the Department of Health

Cynthia M Loeffler

Augusto C Ochoa

Dan L Longo

Peter M Anderson

Arnold S Leonard

John J O'Shea

Hiromoto Mizuguchi

Walter Urba

Hiromoto Mizoguchi

The present invention provides a liposome comprising an effective immunoadjuvant amount of a lymphokine such as IL-2. Also provided is an effective antineoplastic amount of IL-2 liposomes in combination with adoptively transferred cells stimulated with anti-CD3 monoclonal antibody plus IL-2.

Lipsome containing IL-2

Liposome immunoadjuvants containing IL-2

A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels and T-lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, or a protein in the T lymphocyte signal transduction pathway, and comparing the level to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.

Evaluation and treatment of patients with progressive immunosuppression

The present invention is directed to a method of increasing the in vivo immune response of lymphocytes by stimulating the lymphocytes in vitro in the presence of an anti-CD3 monoclonal antibody for less than about 24 hours to form stimulated lymphocytes; infusing the stimulated lymphocytes into a tumor-bearing mammal; and administering IL-2 to the mammal. As a result of this method, the anti-CD3 stimulated lymphocytes display enhanced immunotherapeutic, e.g., cytotoxicity or lymphokine production, in vivo as represented by a decrease in the number of tumors by at least about 20%.

Short-term anti-CD3 stimulation of lymphocytes to increase their in vivo

A method of determining the level of immunosuppression in a mammal involves determining the level of expression of at least one selected TCR subunit protein, or protein in the T lymphocyte signal transduction pathway, and comparing the level to that found in healthy individuals. The method is useful to identify patients having T lymphocytes capable of activation for autologous adoptive immunotherapy and for identifying agents which cause or reverse immunosuppression.

Evaluation and treatment of patients with progessive immunosuppression

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Bladensburg, MD, United States of America

Cynthia M Loeffler