Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model.
OBJECTIVE
We investigated the effect of intraoperative intrasplenic or subcutaneous vaccination with modified tumor cells on tumor progression in a mouse model.


METHODS
Pre-established B16 melanomas on C57/Bl6 mice were surgically removed; mice were vaccinated intraoperatively with B16 cells transfected with an IL-12-encoding pRSC construct, the empty plasmid, or B16 frozen cells. Cells were given either intrasplenically or subcutaneously. Intrasplenic effects of vaccination were examined along with survival data. Mice without tumor recurrence underwent a second tumor implantation.


RESULTS
Animals administered IL-12 pRSC cells showed significant alterations in the spleen, such as higher percentages of (activated) CD4+ and CD8+ T cells and tumor-specific CD4+ T cells among splenocytes. The tumor recurrence rate after resection ranged from 13 to 36%. Cases with recurrent tumors in particular benefited in all therapy groups, resulting in enhanced (tumor-free) survival, reduced tumor growth and lower metastasis rates. Following macroscopic complete tumor resection, the optimum outcome resulted from vaccination with IL-12 pRSC cells into the spleen and subcutaneously administered frozen cells. Survival times were enhanced in all therapy groups after tumor reimplantation, although results were not significant.


CONCLUSIONS
Intraoperative whole-cell vaccination with autologous tumor cells yields promising data, and could be considered as a future option in adjuvant cancer therapy.
Dietrich
Arne
A
Clinic for Abdominal, Vascular, Thoracic and Transplant Surgery, Leipzig University, Chirurgische Klinik II, Liebigstr. 20, 04103 Leipzig, Germany. arne.dietrich@medizin.uni-leipzig.de
Stockmar
Christoph
C
Aust
Gabriela
G
Endesfelder
Susan
S
Guetz
Anke
A
Sack
Ulrich
U
Schoenfelder
Manfred
M
Hauss
Johann
J
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002452:Cell Count; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005500:Follow-Up Studies; D007267:Injections; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D007432:Intraoperative Period; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology / Q000379:methods; D012680:Sensitivity and Specificity; D013154:Spleen / Q000276:immunology / Q000473:pathology*; D016019:Survival Analysis
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D018664:Interleukin-12