GROWTH OF HUMAN TUMOR-CELL LINES IN IMMUNODEFICIENT SCID AND IMMUNE RECONSTITUTED HUMAN-PBL-SCID MICE - AN IMPROVED IN-VIVO MODEL FOR THE STUDY OF HUMAN MALIGNANCY

To assess the suitability of the SCID mouse as a relevant model of human malignant disease Various human cell lines were transferred to these animals and the ability of these cell lines to grow and develop in vivo carefully characterised. Tumour cells were injected at varying doses via the intraperitoneal, intravenous or subcutaneous routes and the growth pattern and metastasis evaluated by measuring survival time, by macroscopic observation of lesions and by performing histology on major organs and growing transplanted tumours. Using this approach a variety of human cell lines were observed to grow easily and rapidly in SCID mice without any histological evidence of immune rejection by the murine host. In particular, the growth of different human ovarian carcinoma cell lines was highly reproducible at the intraperitoneal site with the dissemination of disease from this site and the pathology of tumours similar to that found in human patients. Further experiments in chimeric human-PBL-SCID mice created by the transfer of human lymphocytes to the immunodeficient host, showed that human ovarian tumours could still be established in reconstituted animals, although with a significant increase in survival time when compared with similarly challenged SCID hosts. The growth of human tumours in human-PBL-SCID mice provides a unique model for the study of the interaction of human lymphocytes with human tumours in vivo and for the development of tumour specific immunotherapies at present either unethical or impractical in human patients.