The German “Fusion” Vaccines: Promising Preliminary Results and Controversy

Vaccine therapies involve injecting the patient with a substance that produces an immune response against the tumors. Unlike vaccines for infectious diseases such as tetanus, small pox, and polio, where the vaccine is used to prevent infection, these vaccines are used to actually treat the disease.

A group of German physicians and scientists have developed two very interesting vaccine therapies for RCC. Both involve fusing tumor cells to immune system cells and using these hybrid cells as a vaccine to stimulate the immune system to eliminate the tumor. Both vaccines have very little in the way of side effects, and both have induced complete responses in some patients with metastatic RCC without any other concurrent therapy such as IL-2 to confound the issue.

The earlier of the two vaccines was created by fusing B-Cells (a type of immune system cell) to tumor cells. The results of treatment of 24 patients with metastatic RCC were accepted for publication in June 1998 and published in October. An abstract on what appears to be an update on the result was presented at a meeting in October 1998. By this time they had treated 32 patients. Side effects were very minimal: A few patients had fevers around the time of the vaccinations. Of the 32 patients 4 (12.5%) had a complete response and three had an temporary partial response. Several others were stable. Response duration is a critical factor, and it was not discussed in the October abstract, however in the full paper published earlier it was reported that two patients had achieved a complete response, one of which was ongoing at 11 months. The other was also ongoing, but with very short follow-up.

There were actually two vaccines used here. In one they used autologous tumor cells (the patient’s own tumor cells). In the other they used allogeneic tumor cells (tumor cells from unrelated patients). It appeared that vaccine made from an unrelated patient’s tumor may have been more effective, but the numbers are very, very small. Most of the patients had been treated unsuccessfully with unspecified “chemotherapy” before they got the vaccine and responses occurred despite this pre-treatment. Often pre-treated patients are less likely to respond to further treatment than patients who have had no other drug treatment.

In March 2000, a German group, including some of the same researchers who did the B-Cell hybrid vaccine, published a paper on clinical results with another hybrid cell vaccine in Nature Medicine. That same issue of Nature Medicine also has an informative commentary by Donald Kufe, MD. At any rate, this fusion cell vaccine uses cells from the patient’s own tumors fused with a special type of immune system cell called a “dendritic cell.” Only 17 patients were treated. Again, side effects were minor – a few patients had temporary fevers and there was some reaction at injection sites. Interestingly, some patients reported pain at metastatic sites. Results were quite promising with 4 complete responses and 3 partial responses. All of the complete responses were ongoing at 10-19 months. Of the partial responders, one patient relapsed after six months, but two others were ongoing at 9 and 21 months. Again the sample size is too small to say if the real response rate is anything like this high – but follow-up is longer than for the B-Cell study and the data suggests some of these responses are holding up. All of the patients in this study had a nephrectomy and, unlike the B-Cell vaccine, most had no prior drug treatment. Interestingly, the one exception, a patient who progressed on IL-2, Interferon, and 5-FU, did achieve a partial response, suggesting this treatment might work even when IL-2 therapy doesn’t work. The authors feel the response to this vaccine was superior to that for the B-Cell vaccine. I think it’s extremely unclear with these very small numbers and the rate of pre-treatment in the B-Cell group. Despite uncertainty about the real response rate to each of these vaccines, it’s pretty clear that some patients do respond.

Given metastatic RCC is such a difficult cancer to treat, this virtually non-toxic approach is certainly very promising – if it can be reproduced. That however is a big “if”. Unfortunately, this study has been the subject of a scientific scandal and these results haven’t yet been reproduced. For more details follow the link below.

References, Trials, and Resources

  • There has been a major scientific scandal over this study. Click Here for the full story.
  • A Phase I/II trial of a very similar approach is now being conducted in Boston by Genzyme Corporation. For details, see my review of Genzyme’s Trial in the Renal Cell Cancer Evaluated Trial Database (the review links back to articles here but also contains additional specific information on the trial.)
  • The way in which this vaccine works is truly fascinating. For a detailed discussion, read my explanation in: How the German Fused Dendritic – Tumor Cell Vaccine Works
  • Fusion Vaccine Abstracts and References

This CancerGuide Page By Steve Dunn. © Steve Dunn
Page Created: January 29, 2003, Last Updated: January 29, 2004