GAMMA-INTERFERON ADMINISTRATION AFTER Y-90 RADIOLABELED ANTIBODY THERAPY - SURVIVAL AND HEMATOPOIETIC TOXICITY STUDIES

Purpose: Hematopoietic toxicity is the dose-limiting factor for radioi mmunotherapeutic regimens. Cytokines have been shown to decrease hemat opoietic toxicity in animals exposed to whole-body irradiation, The pu rpose of this study was to investigate the effects of murine gamma-int erferon (gamma-IFN) on survival and hematopoietic toxicity in mice tre ated with high dose (90)yttrium labeled anticarcinoembryonic antigen ( CEA) monoclonal antibody. Methods and Materials: Balb/c nu/nu mice wer e injected intravenously with 250 Ci Y-90-T84.66 (a murine anti-CEA mo noclonal antibody), Thirty thousand units of gamma-IFN was administere d IV 24 h later, Control mice received either 250 Ci Y-90-T84.66 alone or 30,000 units gamma-IFN alone. Survival, antibody biodistribution, and bone marrow histologic studies were then performed. Results: Only 7% of the animals treated with Y-90-T84.66 survived up to 40 days post treatment, when the study was terminated, In contrast, 52% of the mice treated with both Y-90-T84.66 and gamma-IFN survived 40 days postther apy. No toxic deaths were seen in the control group administered gamma -interferon alone. Histologic examination of the bone marrow of animal s receiving Y-90-T84.66 and gamma-IFN showed cellular depletion of 40- 70% of the hematopoietic cells by 48 h, Cell depletion was 50-70% and 20% by 72 h and 8 days posttherapy, respectively, The marrow of the Y- 90-T84,66-treated control group was depleted to a level of 50-80% at 4 8 h, and remained depleted at 90% at 72 h and 8 days posttherapy. No m arrow cell reduction was seen in the gamma-IFN-only treated group, Bio distribution studies showed no alterations in antibody biodistribution or kinetics that could account for the changes in bone marrow toxicit y after gamma-IFN. Conclusion: These results demonstrate that gamma-IF N can reduce the hematologic toxicity resulting from high dose radioim munotherapy, Histologic studies of bone marrow suggest that gamma-IFN acts primarily to accelerate myelorestoration of the bone marrow, Furt her studies exploring the use of gamma-IFN as an adjunct to radioimmun otherapy are therefore warranted.