Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models

Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several pat ients with multiple-myeloma treated with rHuEpo has shown, in addition to t he improved quality of life, a longer survival than expected, considering t he poor prognostic features of these patients, Based on these observations, we evaluated the potential biological effects of rHuEpo on the course of t umor progression by using murine myeloma models (MOPC-315-lgA lambda (2) an d 5T33 MM-1gG(2b)), Here we report that daily treatment of MOPC-315 tumor-b earing mice with rHuEpo for several weeks induced complete tumor regression in 30-60% of mice. All regressors that were rechallenged with tumor cells rejected tumor growth, and this resistance was tumor specific. The Epo-trig gered therapeutic effect was shown to be attributed to a T cell-mediated me chanism. Serum Ig analysis indicated a reduction in MOPC-315 lambda light c hain in regressor mice. Intradermal inoculation of 5T33 MM tumor cells foll owed by Epo treatment induced tumor regression in 60% of mice, The common c linical manifestation of myeloma bone disease in patients with multiple-mye loma was established in these myeloma models. Epo administration to these t umor-bearing mice markedly prolonged their survival and reduced mortality. Therefore, erythropoietin seems to act as an antitumor therapeutic agent in addition to its red blood cell-stimulating activity.