Use of hematopoietic growth factors to control myelosuppression caused by radioimmunotherapy.
Therapeutically efficacious doses of 131I-antibody result in a loss in circulating white blood cells; the granulocyte population is suppressed by 80-85% and the agranulocytes by 60-65% following 2 mCi of 131I-antibody in hamsters. The administration of 100,000 units of human recombinant interleukin 1 24 h prior to radioantibody can prevent the loss in WBC from 1 mCi of radioantibody and reduce the loss from 2 mCi of antibody. Recombinant murine granulocyte-macrophage colony-stimulating factor is also a potent stimulator of myelopoiesis and may also be useful as a method of reducing radioantibody-induced myelosuppression. The tumor uptake of radioantibody in animals treated with recombinant interleukin 1 is reduced by 30% 1 day after injection of radioantibody but returns to levels seen in animals not treated with the cytokine at 96 and 168 h. Therapeutic efficacy is not compromised by doses of interleukin 1 used to prevent myelosuppression. Therefore, the use of cytokines will permit the use of higher doses of radioantibody for greater tumor therapy with less myelotoxicity than in the absence of cytokine treatments.
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
R D
RD
Blumenthal
R M
RM
Sharkey
L M
LM
Quinn
D M
DM
Goldenberg
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects*; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D006224:Cricetinae; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000633:toxicity*; D007958:Leukocyte Count; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor