Paclitaxel saves rat heart allografts from rejection by inhibition of the primed anti-donor humoral and cellular immune response: implications for transplant patients with cancer.
Paclitaxel is an anti-neoplastic drug that was recently shown also to have immunosuppressive properties in naïve rat heart transplant recipients. Here, we tested whether paclitaxel could also effectively reverse an ongoing immune response in transplant recipients. We therefore used a model in which Lewis rat recipients receiving ACI rat heterotopic heart allografts were: (1) untreated, or treated with either (2) paclitaxel or (3) cyclosporine, starting 5 days after transplantation. Allograft survival was determined in one group, and in a second group cytotoxic T-lymphocyte (CTL) responses were determined and serum anti-donor cytotoxic antibody levels were measured. Results showed that paclitaxel was as effective as cyclosporine in saving recipients from imminent allograft rejection. Immunologically, paclitaxel reduced the allogeneic-CTL response, but most impressively, the cytotoxic antibody response was nearly eliminated in saved recipients. Therefore, paclitaxel's immunosuppressive properties, along with its known effectiveness against a wide variety of tumors, makes it potentially useful for the simultaneous treatment of rejection and neoplasms in cases of transplant-related cancer.
Tange
Stefan
S
Department of Surgery, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
Scherer
Marcus N
MN
Graeb
Christian
C
Andrassy
Joachim
J
Justl
Martin
M
Frank
Erika
E
Jauch
Karl-Walter
KW
Geissler
Edward K
EK
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014019:Tissue Donors; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D000972:Antineoplastic Agents, Phytogenic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D017239:Paclitaxel