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Vaccination Strategy with Hybrid Cells Shows Promise in Renal Cell Carcinoma: Presented at AACR

By Paula Moyer

ANAHEIM, CA -- April 25, 2005 -- A vaccine based on a hybrid of dendritic and tumor cells shows promise for treating patients with renal cell carcinoma, according to a team of investigators who presented findings here at the 96^th annual meeting of the American Association for Cancer Research.

"Although this was a trial to establish safety, some of the patients had a clinical response," said principal investigator Yanzhang Wei, PhD, assistant director, Oncology Research Institute, Greenville Hospital System, Greenville, South Carolina, United States. "One patient had a partial remission that continues 2 years after treatment."

He and his co-investigators developed a technology that purifies the hybrid, known as dendritomas, which are made from a fusion mixture of the two types of cells. Dr. Wei said that with this system, he and his co-investigators dye the dendritic cells and tumor cells with dyes of various colors. After fusion, those that have a third color are the hybrids and are then sorted out for use in vaccination.

Earlier research showed that the dendritoma vaccination bypassed some of the major toxicities seen in vaccine therapy and also induced some immunological and clinical responses that were specific to certain tumor cells.

Therefore, the team designed a pilot study to test its feasibility in renal cell carcinoma. They analyzed the data on seven patients with stage IV renal cell carcinoma and are awaiting the data on an additional four patients.

The dendritomas were made from the patient's autologous dendritic and tumor cells, which the patient received by subcutaneous injection. Within 5 days after the first vaccination, the patients received three escalating doses of interleukin-2, which consisted of 3, 6, and 9 million units, respectively.

The investigators documented 17 Grade 1 adverse events and one Grade 2 event, with no Grade 3 or 4 events. The most common Grade 1 adverse events were skin flushing and rashes, along with erythema, chills, joint stiffness in the hands swollen tumor lesions, and lethargy. One patient had a Grade 2 erythema of the eye.

To determine whether the vaccine stimulated a tumor cell-specific immune response, the investigators used flow cytometry to analyze the percentage of T cells that expressed interferon-gamma. All

They found that all patients had an increase of interferon gamma-expressing CD4+ T cells after they were vaccinated. In addition, six patients had an increase in interferon gamma-expressing CD8+ T cells.

One patient had a partial response and three had stable disease after vaccination. One patient died of renal cell carcinoma within 12 weeks, while of the remaining six, one had a partial remission, three had stable disease, and two had disease progression.

The six patients who have since died did so within an average of 254 days after vaccination. The range of time to death after vaccination was 67 to 582 days. The remaining patient has lived disease-free for more than 2 years.


[Presentation title: A pilot study of dendritoma vaccine for stage IV renal cell carcinoma. Abstract 3465]

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