Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer
| Status: | Suspended |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/18/2016 |
| Start Date: | May 2008 |
| End Date: | December 2018 |
Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer
The purpose of this study is to collect data on the safety and effectiveness of 2nd
generation designer T cells in patients with breast 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 to the participant so that they can attack and kill tumor cells.
generation designer T cells in patients with breast 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 to 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.
For the Phase Ia component, patients receive a single dose of gene-modified autologous T
cells on this dose-escalation trial. Doses are 10^9 and 10^10 modified T cells. Patients are
monitored for safety and response. Patients are on-study for one month after dosing.
For the Phase Ib component, patients receive a fixed dose of gene-modified T cells (10^11
cells), randomized to receive T cell growth factor interleukin 2 (+IL2) [Experimental] or
not (-IL2) [Control]. The IL2 is administered outpatient by continuous infusion for a
two-week period. On Day +2 and Day +10, the patient's tumor is biopsied to assess the
designer T cell presence in the tumor as a means of judging the benefit of added IL2.
Patients will also be followed for tumor response.
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.
For the Phase Ia component, patients receive a single dose of gene-modified autologous T
cells on this dose-escalation trial. Doses are 10^9 and 10^10 modified T cells. Patients are
monitored for safety and response. Patients are on-study for one month after dosing.
For the Phase Ib component, patients receive a fixed dose of gene-modified T cells (10^11
cells), randomized to receive T cell growth factor interleukin 2 (+IL2) [Experimental] or
not (-IL2) [Control]. The IL2 is administered outpatient by continuous infusion for a
two-week period. On Day +2 and Day +10, the patient's tumor is biopsied to assess the
designer T cell presence in the tumor as a means of judging the benefit of added IL2.
Patients will also be followed for tumor response.
Inclusion Criteria:
- Must have cancer of the breast
- 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)
Exclusion Criteria:
- Requiring systemic steroids
- Serious medical conditions
- Concurrent malignancies
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2
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