Human colon adenocarcinoma in the SCID/CB6 radiation chimera is susceptible to adoptive transfer of allogeneic human peripheral blood mononuclear cells.
The aim of this study was to develop a murine model of human colon carcinoma (hCC) and to ascertain the potential of cellular immunotherapy in this model. Fragments of hCC obtained at surgery from 6 patients were transplanted under the kidney capsule of lethally irradiated CB6 mice radioprotected with severe combined immunodeficient (SCID) mice bone marrow. Tumor xenografts conserved their malignant behavior in the new environment, invading the mouse kidney parenchyma and expanding into the peritoneal cavity and adjacent tissues. Their growth was typically exponential, and they expanded to dimensions that allowed their subsequent fragmentation and passage to further preconditioned mice. Human carcinoembryonic antigen (hCEA) was detected on the implanted tumor and at occasionally spontaneous lung metastases. Most significantly, high levels of this tumor marker were detected in the sera of tumor-bearing mice, providing a useful tool, which allowed long-term experiments, monitoring of tumor progression, and its response to some treatment modalities. For instance, complete resection of the transplanted tumors, by means of nephrectomy, resulted in the disappearance of hCEA from mice sera within 2 weeks. Similarly, adoptive transfer of allogeneic human peripheral blood mononuclear cells (PBMC) into the peritoneum of tumor-bearing mice, resulted in their rapid engraftment, infiltration of tumor mass, and a significant drop of hCEA levels in mice serum, accounting for inhibition of tumor growth. We suggest that this novel model of human colon carcinoma affords the opportunity for in vivo evaluation of different preclinical treatment modalities, particularly, those involving manipulation with immune effector cells.
Arditti
Fabian D
FD
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Greenberg
Ron
R
Dekel
Benjamin
B
Marcus
Hadar
H
Nagler
Arnon
A
Berrebi
Alain
A
Skornick
Yehuda
Y
Reisner
Yair
Y
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016026:Bone Marrow Transplantation; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009392:Nephrectomy; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous; D016896:Treatment Outcome