The impact of intraoperative vaccination with IL-12 modified autologous tumor cells in the Lewis lung carcinoma mouse model.
OBJECTIVE
To improve immunological defense of tumors, we investigated the effect of intraoperative vaccination with IL-12 cDNA transfected cells in an autologous mouse tumor model.


METHODS
Tumors derived from autologous Lewis lung carcinoma cells were established in C57/BL6 mice. At day seven, the tumors were surgically removed. Simultaneously, the mice were vaccinated intraoperatively with Lewis lung carcinoma cells transfected with an IL-12-encoding pRSC construct or with the empty plasmid, or with dead cells either intrasplenically (i.s.) or subcutaneously (s.c.). Control mice did not obtain vaccination. Tumor re-growth, survival, and metastasis were monitored. Mice with no tumor re-growth underwent a second tumor implantation. The same parameters were examined.


RESULTS
After tumor resection and vaccination tumors reappeared in 60.0% of the animals of the control group. Lowest tumor reoccurrence rates of 41.4 and 43.5% were seen in animals receiving IL-12 pRSC cells either i.s. or s.c. Survival tended to be enhanced in all vaccinated animals compared with the control group. Following R0 tumor resection, the rate of tumor-free survivors was highest when IL-12 pRSC cells were given i.s. (73%, control 45%). 37-59% of the mice of the therapy groups did not develop a tumor, that is, they were tumor-free survivors. These mice underwent a second tumor implantation 120 days after tumor resection and vaccination. Tumor growth was significantly delayed in mice receiving IL-12 pRSC cells.


CONCLUSIONS
Intraoperative autologous whole-cell vaccination is practicable and proved to have anti-tumor potential, and therefore, it could be an additional option in adjuvant cancer therapy.
Department of Surgery, Clinic for Abdominal, Vascular, Thoracic and Transplantion Surgery, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany. arne.dietrich@medizin.uni-leipzig.de
Arne
A
Dietrich
Christoph
C
Stockmar
Susan
S
Endesfelder
Anke
A
Guetz
Gabriela
G
Aust
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D007430:Intraoperative Care; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D014162:Transfection / Q000379:methods
D019496:Cancer Vaccines; D018664:Interleukin-12