TKCTM is our adjuvant treatment combining standard-of-care chemotherapy plus gene therapy using the Herpes simplex virus (HSV) thymidine kinase-encoding gene (Ad-tk) and the antiherpetic drug Prodrug in the treatment of cancers.  TKCTM is currently being used in the Ovarian cancer trial.    In Ovarian cancer the initial chemotherapy usually includes the drugs cisplatin or carboplatin in a regimen combined with taxol or cyclophosphamide, as those drugs are highly active against this tumor and 73% of the patients with Stage III and IV respond to this therapy.  This initial treatment response does not translate into a favorable long-term prognosis.  Treatment results depend on the ability to surgically remove as much tumor as possible, and on the location of the remaining tumor.  In addition, patients who relapse following the initial chemotherapy only have a 10-20% response rate to second line therapy, which has not been shown to prolong patient survival. 

Considering these unsatisfactory treatment results, alternative therapeutic approaches are necessary to improve long-term survival of patients with ovarian cancer.  This investigational new drug application describes a proposed Phase I study designed to study the safety and toxicity profile of intraperitoneal gene therapy for patients with locally recurrent ovarian cancer after failure of combined radical surgery and chemotherapy.  These patients do not have any standard treatment available to them that would demonstrate a high degree of efficacy in eradicating the tumor with a reasonable degree of safety.

We have also studied the interaction of gene therapy and chemotherapy and found that the adenovirus-mediated thymidine kinase gene therapy can enhance sensitivity of ovarian cancer cells to selected chemotherapeutic agents.  Concomitant combined gene therapy and chemotherapy achieved the best treatment effect.