Human Flt3 ligand from Pichia pastoris inhibits growth of lymphoma and colon adenocarcinoma in mice.
Potent effects of Flt3 ligand (FL) on the development of the immune system have generated much interest in application of FL in cancer immunotherapy.


OBJECTIVE
To evaluate the effects of Pichia pastoris secreted rhFL on the growth of mouse EL-4 lymphoma and C26 colon adenocarcinoma injected in syngeneic mice for the first time.


METHODS
Mice were placed into one of two treatment groups. 2 x 10(5) EL-4 or C26 cells were injected subcutaneously (SC.) into mice on day 0. Group 1 received subcutaneous PBS injections from Day -7 to Day 14 and group 2 received subcutaneous rhFL injections at 30 microg/day from Day -7 to Day 14. Serial tumor areas were measured. On Day 22, mice from each group were sacrificed, and weight of tumors and spleens were evaluated. Data analysis used Student t tests.


RESULTS
Pichia pastoris secreted rhFL resulted in tumor growth delay for both EL-4 lymphoma and C26 colon adenocarcinoma compared with control (P < 0.01). Tumors from rhFL-treated mice were smaller (P < 0.01) than controls while spleens larger (P < 0.01) than controls. Histological examination of tumor sections revealed an obvious increase in regions composed largely of infiltrating cells in the rhFL-treated tumors. Infiltrating cells could be detected in clusters among tumors from mice treated with rhFL whereas these cells were only occasionally detected in sections of control tumors.


CONCLUSIONS
Treatment of rhFL expressed from Pichia pastoris resulted in an antitumor response against EL-4 and C26 tumors injected in syngeneic mice.
Zhang
Yan-Li
YL
National Laboratory of Medical Molecular Biology, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005 P. R. China. zhyanli@gmail.com
Wei
Yi-Ju
YJ
Deng
Yan-Chun
YC
Wang
Ya-Dong
YD
Liu
Chang-Zheng
CZ
Su
Lin
L
Yang
Ke-Gong
KG
Chen
Song-Sen
SS
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007167:Immunotherapy; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010843:Pichia / Q000737:chemistry*
D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; C084881:flt3 ligand protein