The applicant has recently developed in nude mice orthotopic metastasizing onplant models for colon, bladder, head and neck, stomach and pancreas cancers. He proposes to utilize severe combined immunodeficient (scid) mice to develop subsequent models for the development of immunotherapeutics utilizing in part technology that he has developed for the onplant metastasizing orthotopic models in nude mice. To study the feasibility of such a development in Phase I, he will first attempt to determine the take rate, orthotopic growth and metastasizing capability of human colon tumors onplanted to the colon in scid mice. He will then reconstitute the scid mice with human peripheral lymphocytes in varyingamounts from human donors that are Epstein-Barr virus sero-negative. After determining the success of the reconstitution, he will then orthotopically onplant human colon tumors as he did for nude mice and the unreconstituted scid mice to determine the take rate in the reconstituted scids and compare it with the take rates in nude mice and unreconstituted scids. If the take rate is comparable in all three models, this will allow in Phase II the development of onplant orthotopic metastasizing models for the major human cancers in scid mice.
Furukawa, T; Kubota, T; Watanabe, M et al. (1993) A novel ""patient-like"" treatment model of human pancreatic cancer constructed using orthotopic transplantation of histologically intact human tumor tissue in nude mice. Cancer Res 53:3070-2 |