JANUARY 2008 PROGRESS REPORT FROM DR. BRENTJENS
1. The initiation of a
clinical trial utilizing genetically targeted patient T cells to treat pati=
ents
with chemotherapy-refractory CLL.
The main= focus of our research program is to develop novel approaches for the treatment of CLL. Specifically, using gene therapy techniques, we have developed a means of genetically altering a patient’s own immune cells (called T cells) to recognize a protein (called CD19) which is present on the surface of CLL tumor cells. In the laboratory, these modified T cells can recognize and kill a patient’s CLL tumor cells. More significantly, in mice, we ha= ve found that such T cells can cure mice from tumors which express the CD19 antigen.
Based on= these promising studies, we have initiated a Phase I trial to study whether we can generate these tumor killing immune cells from patients with CLL, and test = the efficacy and safety this treatment approach. While the process of obtaining FDA approval for this study was lengthy, we received the go-ahead to begin this trial roughly 6 months ago. To date, we have treated 2 patients with at the lowest dose of modified cells. Neither patient experi= enced significant side effects while both developed transient decreases in tumor size and decreases of tumor cells in the blood.&nbs= p; Although promising at this early stage, we hope for even better resu= lts as we treat patients at higher more clinically relevant doses of modified cells. I look forward to keep= ing the CLL Foundation updated on this trial in the future.
2. Generation of a CLL
patient data base of peripheral blood and serum samples.
The main=
focus
of our proposal to the CLL foundation was to generate and test a robust data
base of patient T cell and tumor cell samples. I’m pleased to report that t=
he
data base currently has 42 samples from different CLL patients at all stage=
s of
disease. Furthermore, based on
serum samples analyzed from patients enrolled in the clinical trial, we have
made interesting observations on distorted levels of immune signaling prote=
ins
(termed cytokines) in patients with CLL.&n=
bsp;
To this end, we have modified our blood sample collection to include
collection of serum samples and we are in the process of analyzing these
samples to assess cytokine levels in blood samples from CLL patients in
comparison with healthy donor samples. We hope that these studies may give
critical insight into the mechanisms of immune dysfunction in patients with
CLL. Furthermore, we have uti=
lized
CLL foundation funds to generate retroviral stock to study whether T cells =
from
patients with CLL are equally susceptible to gene therapy when compared to T
cells from normal donors. Significantly, data generated from =
these
studies are being combined with those generated from the clinical trial.
3. Optimizing gene th=
erapy
of T cells in patient samples.
I am further pleased to r= eport that funding from the CLL foundation has enabled us to conduct a series of studies designed to optimize our ability to genetically modify T cells. These studies have been critical t= o the clinical trial. The significa= nce of these experiments is reflected in the fact that these studies were recently published in a leading gene therapy journal (Human Gene Therapy). In light of the foundation’s support of these studies, the CLL foundation was cited in the acknowledgeme= nts. I have attached a copy of this manuscript for your and the foundation’s review.
Renier Brentjens MD PhD
Assistant Member
Leukemia Service
Department of Medicine
(212) 639-7053