Colorectal Cancer Vaccine May Boost Survival

PARIS--Nearly 90% of patients with resected Dukes B and C colorectalcarcinoma were still alive 3 years after active specific immunizationwith a new autologous tumor vaccine, researchers from the GermanCancer Research Center, Heidelberg, and the University Hospital,Mannheim, Germany, have found.

V. Schirrmacher, PhD, of the Heidelberg center, presented thefindings at the Eighth Annual European Cancer Conference (ECCO-8).

To prepare the colorectal cancer vaccine, purified and inactivatedcells from the patient's own tumor are incubated with the NewcastleDisease Virus (NDV), a chicken virus with unique antitumor andimmune-stimulating properties.

The virus binds almost immediately to the cancer cells and beginsreplicating within 4 hours, Dr. Schirrmacher said. Transfectionof the tumor cells with the virus bolsters their antigen-presentingcapacity so that, after inoculation, the patient's immune responseis mobilized against his or her own cancer cells.

Noting that immune reactivity, as reflected by delayed hypersensitivityskin reactions, increases after each successive inoculation, hesuggested that the strength of this reaction may forecast a morefavorable clinical outcome.

After charting the clinical course of 48 patients who receivedthree doses of the NDV vaccine at 2-week intervals, starting 6to 8 weeks after surgery, the Heidelberg-Mannheim team documentedsurvival rates of 98% at 2 years and 88% at 3 years. Three-yearoverall survival was 86% in patients with Dukes B colon cancer,88% in Dukes C colon cancer, 93% in Dukes B rectal cancer, and88% in Dukes C rectal cancer.

In comparison, Dr. Schirrmacher said, 2-year survival was 74%in a historical control group of more than 600 patients treatedwith surgery alone, and only 67% in nine patients who receivedan experimental vaccine made with BCG (Bacillus Calmette Guerin).Side effects of the NDV vaccine were limited to induration anderythema at the inoculation site, in contrast to the persistentulceration observed after injection of the BCG vaccine.

As the next step, Dr. Schirrmacher urged prospective, randomized,controlled trials of the NDV vaccine in patients with resectedcolorectal cancer. "A US study has suggested that adjuvantchemotherapy with 5-fluorouracil and levamisole gives additionalimprovement in survival, and it is against this that immunotherapymust be compared, which makes protocols more difficult,"he said.

Dr. Schirrmacher mentioned that colorectal cancer may not be theonly promising tumor candidate for NDV autologous tumor vaccines.

Preliminary results from the Urology Clinic at the HeidelbergCenter have revealed that an autologous NDV vaccine, coupled withsystemic interleukin-2 and interferon-alfa, produced a completeor partial response in one third of patients with renal carcinoma,he said, and that all responders to the regimen survived for atleast 4 years (Pomer et al: Int J Oncol 6:947-954, 1995).