HAMBURG, Germany ¿ The concept of immune therapy against cancer appears to be paying off. In Germany, clinical trials of therapeutic vaccines against metastatic renal cell carcinoma and breast cancer have shown favorable results in Phase I trials.
In a clinical trial conducted by the University Clinic of Gottingen, 17 patients in advanced stages of the disease and showing metastases in brain, bone, liver and lung were treated over a period of two years with consecutive injections of a novel vaccine prepared by electrical fusion of autologous tumor cells and allogeneic dendritic cells.
The participants got an initial inoculation of the vaccine, followed by a second shot six weeks later. Unless the cancer worsened, booster shots were given every 12 weeks. Four of the patients achieved complete remission of the cancer and have had no evidence of cancer for up to 21 months, and three showed partial remissions or a mixed response. In two others, tumor growth came to a halt. With usual radiation and interferon treatments, response rates are less than 10 percent.
¿This is an example of an individualized immune therapy,¿ Gerhard Anton M|ller, nephrologist and one of the authors of the study, said. ¿By using autologous tumor cells, patients with all HLA haplotypes can be successfully immunized. In principle, the strategy can be used against other tumors as well. However, these findings are preliminary results, and we have to wait until a comparative study is finished. But clearly we have demonstrated that the vaccination is safe and effective.¿ The findings were published in the March issue of Nature Medicine.
Another example of a successful immune therapy was presented last week by a research group at the University Medical Clinic of Tubingen in Germany. The scientists observed a therapeutic effect in a Phase I trial involving 10 breast cancer patients. The group used a concept developed by Stefan Stevanovics of the university¿s Interfaculty Institute for Cell Biology. Stevanovics studies peptides that are generated inside human cells by protein breakdown and taken up by major histocompatibility complex (MHC) molecules, a crucial component of the immune system. After take-up, the peptides are displayed at the cell surface by the MHC complex to the T lymphocytes, which trigger an im mune reaction against cells displaying unknown peptides.
Stevanovics was able to uncover for several thousand peptides the rules by which they are chosen by MHC molecules for display. The findings have been entered into a database that is accessible by other researchers via the Internet. ¿Using the database, we are able for a given protein to forecast in 80 percent of all cases which peptides are displayed by which MHC molecules,¿ Stevanovics said.
As cancer cells very often contain proteins not found in normal cells, Stevanovics used the database to identify peptides that were presented by MHC molecules in tumor cells containing a variant of the Mucin 1 protein. This variant is typical for breast cancer cells.
For the trial these peptides specific for the breast cancer form of Mucin 1 were loaded onto dendritic cells derived from patients' blood. After vaccination, specific T lymphocytes were formed in five of 10 patients. In one of the five, metastasis recessed, while in the others tumor growth came to a halt. The patients suffered from breast and ovary cancer and already had undergone radiation and chemo therapy.