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 patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic features of these patients. Based on these observations, we evaluated the potential biological effects of rHuEpo on the course of tumor progression by using murine myeloma models (MOPC-315-IgAlambda(2) and 5T33 MM-IgG(2b)). Here we report that daily treatment of MOPC-315 tumor-bearing 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-triggered therapeutic effect was shown to be attributed to a T cell-mediated mechanism. Serum Ig analysis indicated a reduction in MOPC-315 lambda light chain in regressor mice. Intradermal inoculation of 5T33 MM tumor cells followed by Epo treatment induced tumor regression in 60% of mice. The common clinical manifestation of myeloma bone disease in patients with multiple-myeloma was established in these myeloma models. Epo administration to these tumor-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.
Mittelman
M
M
Department of Medicine, Rabin Medical Center, Hasharon Hospital, Petach-Tikva 49100, Israel.
Neumann
D
D
Peled
A
A
Kanter
P
P
Haran-Ghera
N
N
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D018450:Disease Progression; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D012074:Remission Induction; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology
D006454:Hemoglobins; D007146:Immunoglobulin lambda-Chains; D004921:Erythropoietin