Genetically modified cells expressing a TGF.beta. inhibitor, the cells being lung cancer cells

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Lung cancers account for 30% of all death due to cancer in the United States (Ramanathan and Belani, 1997).
The overall cure rate for lung cancer is 13% and the current prognosis for patients with non-small cell lung (NSCLC) and small cell lung cancer (SCLC) remains poor.
It has been documented that patients with progressive tumor growth have impaired immune function (Jakowlew et al.
1995, Ransohoff et al 1991; Holladay et al.
1992a; Holladay et al.
1992b).
This impairment, commonly characterized as marked immune hyporesponsiveness, is not solely confined to tumor specific immunity, but rather, is often observed throughout the immune system.
Impairment is especially evident in the cell-mediated or T-cell compartment and is characterized by T-cell lymphopenia and impaired T-cell responsiveness to both tumor specific and non-tumor specific stimuli (Ransohoff et al.
1991).
One way tumors may escape immune surveillance is by expressing lower levels of MHC Class I and Class II molecules.
Other tumors may escape by increasing the expression of immunosuppressor molecules, such as the TGF.
beta.
s.
It is common to observe tumors utilizing a combination of these mechanisms.
Gene therapy has received considerable attention in recent years.
Vaccination with tumor cells designed to augment tumor antigen presentation and induce specific anti-tumor immunity has yielded promising but limited results (Holladay et al.
1992).
Advances in our understanding of cancer biology and developments in vector technologies are advancing the therapeutic potential of tumor vaccine approaches.
It is now possible to genetically modify tumor cells for vaccination to express specific tumor suppressor genes, immune modulators, drug sensitive genes and antisense gene fragments (Huber et al.
1991; Culver et al.
1992; Trojan et al.
1992; Dranoff et al.
1993; Ram et al.
1993; Trojan et al.
1993; Swisher et al.
1999).
In particular preclinical and clinical studies demonstrate the potential of gene therapy approaches in treating lung cancer