Immunotherapy of cancer through expression of truncated tumor or tumor-associated antigen

Abstract

DNA constructs for truncated forms of cancer-specific or cancer associated antigens are included in plasmid or viral expression vectors. The rationale to use constructs for truncated and not for full-size molecules is to eliminate side effects (toxicity, signal transduction etc.) arising from expressed proteins and/or, in cases where such molecules are expressed on the membrane, secreted, or released in the extracellular environment, to prevent formation of antibodies against them. The extracellular portion of the human prostate specific membrane specific antigen (XC-PSMA) has been cloned. Patients were treated either by injection of DNA coding for XC-PSMA in a mammalian expression vector under the CMV promoter or/and by a replication-defective adenoviral vector (Ad5)hat contains an expression cassette for the XC-PSMA. In a third method dendritic cells are isolated from a patient and are treated by exposure to the plasmid or adenovirus used in the previous two treatments. The dendritic cells are then injected into the patient. In some patients, the progression of metastatic prostate cancer is retarded or stopped.

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