Autologous tumor vaccine lowering postsurgical recurrent rate of hepatocellular carcinoma.
OBJECTIVE
A tumor vaccine consisting of formalin-fixed hepatocellular carcinoma (HCC) tissue fragments, biodegradable sustained-releasers of granulocyte-macrophage-colony stimulating factor (GM-CSF) and interleukin-2 (IL-2), and an adjuvant was developed. The aim of this study was to evaluate the effects of autologous tumor vaccine for protective immunity against HCC.


METHODS
C57BL/6J mice were immunized intradermally with the Hepa1-6 tumor vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa1-6 cells. On day 21, the tumor volumes were measured and the effect of tumor vaccine was evaluated. Lymphocytes from the immunized mice were cultured and the specific cytotoxicity against Hepa1-6 was accessed. Then from March 1999 to June 2003, 67 patients with HCC undergoing curative resection were randomly divided into a tumor vaccine group (n = 32) and a control group (n = 35). Patients in the tumor vaccine group received 3 vaccinations at a 2-week interval and the control group only adjuvant treatment for symptoms. A delayed-type-hypersensitivity test was performed before and after vaccination. Primary endpoint was time to first recurrence and recurrent rates were analyzed.


RESULTS
The tumor vaccine protected 87% of syngeneic mice from Hepa1-6 cells inoculation. In an in vitro experiment, splenocytes from the vaccinated mice exhibited a 56% lytic activity against the Hepa1-6 cells at an effector/target (E/T) ratio of 5, whereas they did not exhibit such activity against other tumor cells. The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class II monoclonal antibodies but not with anti-CD4 and anti-MHC-class I antibodies. In clinical trial, thirty-two patients had completed the tumor vaccine procedure and no essential adverse effect occurred. The follow-up averaged 33.6 months (range from 15 to 54 months). The recurrent rate was significantly better in the tumor vaccine group (1 year, 12.6%; 2 years, 35.9%; 3 years, 54%) than in the control group (1 year, 31.6%; 2 years, 61.3%; 3 years, 72.1%; P = 0.037). 23/32 patients developed a DTH response against the fragments of HCC and DTH-response-positive patients had a lower recurrent rate than DTH-response-negative patients (7/23 vs. 5/9).


CONCLUSIONS
The autologous tumor vaccine is a promising adjunctive modality to prevent recurrence of human HCC.
Peng
Baogang
B
Department of Hepatobiliary Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China. pengbaogang@tom.com
Liang
Lijian
L
Chen
Zubing
Z
He
Qiang
Q
Kuang
Ming
M
Zhou
Fan
F
Lu
Mingde
M
Huang
Jiefu
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D045744:Cell Line, Tumor; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D013997:Time Factors
D019496:Cancer Vaccines