Category:

Vaccine,Gene Therapy

Description:

Provided is a method to genetically engineer human lymphocytes, to enable expression of an antioxidant enzyme, which can render the cells resistant to immune suppression mediated by reactive oxygen species (ROS).

Adoptive immunotherapy of patients with advanced cancer or viral infections has so far met with positive, but limited success. This limited therapeutic effect of adoptively transferred lymphocytes may be attributable in part to elimination of Natural Killer cell and T cell activities by oxidative stress. Systemic administration of drugs that strengthen the patient's resistance to ROS is limited by several factors: Drugs have difficulty penetrating into tumors, can cause toxicity due to the relatively high dosages needed to reach the necessary concentration in the tumor or virus infected tissue, and most drugs have a limited half-life.

Dr. Nishimura (Medical University of South Carolina) and his collaborators at the Karolinksa Institutet have developed a method to overcome these problems through "arming" the patients lympocytes (the so called T-cells and NK-cells) through genetic modification with an antioxidant enzyme (catalase) which can neutralize ROS. A patient's own lymphocytes are transduced with a viral construct coding for catalase. This procedure is done ex vivo in a test tube. The modified lymphocytes can then be transferred back to the patient.

Because the modified lymphocytes are now more resistant to ROS, they are protected from cell death and have an enhanced capacity to recognize virus-expressing target cells. They will be able to actively migrate into tumor tissues and have the potential of replicating and remaining in the host for prolonged periods of time.

Potential Applications:

Treatment of viral infections or cancer.

Catalase transduction of T cells can be combined with existing gene-therapy strategies.

Inventor(s):

Drs. M. Nishimura, R. Kiessling, M. Hanson.

Patent Status:

Provisional Patent Application filed

Availability:

Available for:
exclusive
non-exclusive
licensing.

Technology Status:

Preclinical

Licensing Contact:

Ryan N. Fiorini, MBA, Ph.D.
MUSC Foundation for Research Development
PO Box 250828
Charleston, SC 29425
843.876.1906
fiorinir@musc.edu