Immunotherapy: enlisting the immune system to fight cancer

“Higher doses of ipilimumab combined with the GVAX vaccine is showing a lot of success in increasing anti-tumor activity in these patients,” said Saskia J.A.M. Santegoets, Ph.D., a researcher in the Department of Pathology and Division of Immunotherapy at the Vrije Universiteit Medical Center in the Netherlands. “We’re encouraged by the results of this phase I trial and expect ongoing analyses to yield more valuable data about the GVAX/ ipilimumab combination.”

In this trial, the vaccine was administered with escalating doses of anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab. Researchers believe that the combination of these two immunotherapies increases one’s immunity to prostate cancer.

Twelve patients were enrolled in this study. All were given the same doses of GVAX (a 500 million cell first dose followed by bi-weekly 300 million-cell doses for 24 weeks), and, in groups of three, different quantities of ipilimumab administered every four weeks (.3mg, 1mg, 3mg, or 5 mg).

Anti-tumor activity was seen in five of the six patients who received the two highest doses of ipilimumab, including PSA-level declines of greater than 50 percent; these PSA declines were maintained in four of these patients for at least six months, and up to 16 months. Among the patients with PSA-level declines, researchers noted complete resolution of multiple lesions on bone scans in two patients, resolution of cancer spread to abdominal lymph nodes in one patient, and improvement in bone pain in one patient.

The ongoing phase I trial of this combination has enrolled an additional 16 patients with hormone-resistant prostate cancer into an expansion cohort.

Evidence of Efficacy of Antibody Directed Enzyme Prodrug Therapy (ADEPT) in a Phase I Trial in Patients with Advanced Carcinoma: Abstract LB-200

A two-step drug therapy that selectively targets tumors may hold promise for some patients with advanced cancers, according to results of a clinical trial directed by researchers in London.

Scientists at the University College London’s Cancer Institute and the Royal Free Hospital used a technique called antibody-directed enzyme prodrug therapy (ADEPT) in 43 patients with previously treated, advanced colorectal, gastro-esophageal, breast, gallbladder, peritoneal, appendix, or pancreatic cancers, or cancers of unknown primary site. The patients received one, two or three ADEPT treatments over a period of two to 10 days, at dosages ranging from 37 mg/m2 to 3,226 mg/m2.

“We found clinically significant responses in 44 percent of patients,” said senior author Richard H. Begent, M.D., professor of oncology at the University College London’s Cancer Institute. “These results support the case for conducting a randomized phase II clinical trial.”

ADEPT is a two-step treatment for cancer that uses an antibody to carry an enzyme directly to the cancer cells. First, an antibody is given with an enzyme attached. Next, a prodrug (inactive anti-cancer drug) is administered. When the prodrug comes in contact with the enzyme, the resulting chemical reaction activates the anti-cancer drug, which is then able to destroy cancer cells while sparing nearby healthy tissue.