Research Success

CLL patients often develop weakened immune systems, particularly after treatment. This puts CLL patients at greater risk of infectious complications. It is hypothesized that an infusion of stimulated T-cells, given after treatment, may lower the chance of infections.

A Phase I multi-center trial is now open, evaluating whether laboratory processed T-cells will help CLL patients’ immune system recover faster after chemotherapy. Both the University of Pennsylvania (UPenn) and MD Anderson Cancer Center (MDACC) are currently enrolling patients. 

For this trial, a patient’s T-cells are collected prior to initial treatment and frozen until needed. The patient then receives treatment with either fludarabine or alemtuzumab-based chemotherapy. Patients that respond to chemotherapy will be infused with a modified version of their own T-cells once the chemotherapy administration is completed.   In the laboratory, the frozen T-cells are thawed and co-stimulated with CD3/CD28 microbeads and infused back into the patient.

The microbeads contain antibodies which attach to CD3 and CD28 on T-cells and activate and expand them.  By activating the T-cells, the microbeads turn on the anti-cancer and anti-infection activity and allow T-cells to multiply at an accelerated rate.  Properly functioning CD3 and C28 allows the immune system to better fight infection and cancer. 

The trial is being supported by CLL Global’s U.S./European Alliance program.  Drs. Chitra Hosing (MDACC) and Stephen Schuster (UPenn) are chairing the study. The CD3/CD28 microbeads were created and are being supplied by Dr. Carl June (UPenn).  Drs. Elizabeth Shpall (MDACC), Bruce Levine (UPenn), and John Gribben (Barts, UK), are collaborating in the research. 

Similar clinical trials have been conducted in patients with other hematologic malignancies.  These studies show the treatment was well tolerated and results were favorable.  The hope is that CD3/CD28 microbeads will result in rapid immune recovery, reduced rate of infectious complications, and delayed disease progression for CLL patients.

8-Cl-Ado works be depleting CLL cells of the energy they need to function and survive. Also, it is incorporated into the cells’ RNA, rather than DNA. RNA transmits genetic information from the genes to proteins. By targeting the RNA, 8-Cl-Ado inhibits the production of proteins necessary for the CLL cells to survive. These features make 8-Cl-Ado an ideal drug to target CLL cells.

Funds provided by CLL Global were used for toxicology studies required by the Food and Drug Administration before 8-cl-ado could be administered in humans. To date, six patients have been treated with 8-cl-ado. 

One of the goals of CLL Global is that recipients will be able to utilize initial support from the foundation to find other grants to continue the research. Drs. Gandhi and Wierda have subsequently been awarded over $1 million from federal agencies and private organizations to support the clinical study of the 8-cl-ado trial.  CLL Global will share more data from this study as it becomes available.

PEITC is a molecule found in vegetables such as broccoli and watercress. Dr. Peng Huang (MDACC) is turning this molecule into an anti-cancer drug. His laboratory studies have demonstrated that PEITC has strong anti-cancer activity when given in high concentrations.  Presently, the compound is being formulated into capsules to be used in clinical studies.

CLL Global has also supported research being conducted by Dr. Neil Kay at Mayo Clinic using an oral green tea extract. In the initial study, asymptomatic patients were given varying doses of epigallocatechin gallate (EGCG), a major component of green tea. The majority of patients had a reduction in lymphocyte count and decline in lymph node size.  Subsequently, the Mayo researchers have conducted a second study with similar findings. Both PEITC and green tea represent opportunities to use relatively non-toxic treatments to delay and fight cancer growth.