The purpose of this study is to collect data on the safety and effectiveness of 2nd
generation designer T cells in patients with colorectal cancer. Designer T cells are
prepared by collecting white blood cells from the participant, and then modifying these
cells in the laboratory so that they recognize the tumor antigen (CEA). These modified cells
are then given back into the participant so that they can attack and kill tumor cells.
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 surveillance" 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.
Patients receive a single dose of gene-modified autologous T cells on this dose-escalation
trial. Doses are 10^9, 10^10 and 10^11 modified T cells. Patients are monitored for safety
and response. Patients are on-study for one month after dosing.
- Must have cancer of the colon or rectum
- Must have metastatic or unresectable locally advanced disease
- Tumor must express CEA by tumor staining or by elevated serum CEA (>10 ng/ml)
- Must have measurable disease radiologically or by physical exam
- Must have failed potentially curative standard therapy
- Must be 18 years of age or older
- Good performance status (PS 0-1)
- Requiring systemic steroids
- Serious medical conditions
- Concurrent malignancies