Research Group

  • Prof. Edward K. Geissler, Principal Investigator
  • Dr. Markus Guba, Co-Investigator
  • Dr. Markus Steinbauer, Research Associate
  • Dr. Christian Graeb, Research Associate

Location

  • University of Regensburg, Regensburg, Germany

Title

  • Paclitaxel and Rapamycin: A One-Two Punch Against Rejection and Cancer in Organ Transplantation

The success of organ transplantation remains dependent on the use of drugs that suppress a recipient’s immune system from destroying foreign transplanted tissue. Unfortunately, one of the major side effects of suppressing the general immune system is that cancer cells are not as likely to be destroyed by this protective system. Therefore, the occurrence of cancer is a frequent and dreaded side effect of immunosuppressive therapy. This creates a difficult situation, because removal of immunosuppression to reduce de novo neoplasm occurrence puts the organ transplant at risk for rejection. Paradoxically, organ transplants are sometimes done to cure isolated cancer of the liver or lung, but these cancers tend to recur in the transplanted organ, most likely due to the tumor-promoting effect of conventional immunosuppression on residual cancer cells.

In the present study we propose that two specific drugs, rapamycin and paclitaxel, could together have a unique potential to promote allograft survival, while attacking tumor cells. This hypothesis is based on our preliminary data, which shows that the well-known immunosuppressive drug rapamycin can also act to destroy tumors in mice. Additionally, we have also found that the powerful anticancer drug paclitaxel has potent immunosuppressive activity that promotes heart transplant survival in rats. Therefore, we propose to use this "one-two-punch" of rapamycin and paclitaxel to treat tumors in both mice and rats that subsequently receive a heart or liver transplant. In these experiments we will test the protective effect of the "one-two-punch" on the transplanted organ and its potential simultaneous destructive effect against cancer. The mechanisms by which these drugs may complement each other with regard to immunosuppression and tumor growth inhibition are critical, and will be explored. We believe results from this study could have a direct impact on the future successful maintenance of organ transplants in situations where organ replacement is a curative option for early cancer, or when de novo cancer occurs in transplantation patients.