Trial of 2nd Generation Anti-CEA Designer T Cells in Gastric Cancer

T cells can penetrate virtually every biologic space and have the power to dispose of normal
or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous
remissions of cancer. However, T cells are easily tolerized to self or tumor antigens and
"immune surveil¬lance" has manifestly failed in every cancer that is clinically apparent.
It is the goal of this study to supply the specificities and affinities to patient T cells
without regard for their "endogenous" T cell receptor repertoire, directed by
antibody-defined recognition to kill malignant cells based on their expression of antigen.
We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors
to yield "designer T cells" from normal patient cells. Prior studies in model systems
demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen
targets with IL2 secretion, cellular proliferation, and cytotoxicity, the hallmarks of an
effective, self-sustaining immune response. It therefore becomes of paramount interest to
extend these studies to a human system of widespread clinical relevance to explore the
clinical potential of this new technology. The target antigen for these studies is
carcinoembryonic antigen (CEA), which is prominently expressed on tumors of the stomach,
colon and rectum, breast, pancreas and other sites.