Suppression of tumor growth in renal cancer treatment with tumor vaccination after haploidentical bone marrow cell reconstitution.
- Author:
Xi-you WANG
1
;
Zhi-tao WEI
;
Jian-hua HUANG
;
Bao-fa HONG
;
Xin-jing CHEN
;
Hai-yan LÜ
;
Yong YANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Bone Marrow Transplantation; immunology; Cancer Vaccines; immunology; Carcinoma, Renal Cell; immunology; therapy; Cells, Cultured; Disease Models, Animal; Graft vs Tumor Effect; immunology; Kidney Neoplasms; immunology; therapy; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Transplantation Chimera; immunology
- From: Chinese Journal of Surgery 2010;48(17):1328-1331
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate whether whole tumor cell vaccination strategies in combination with bone marrow transplantation (BMT) can stimulate graft-versus-tumor effect (GVT).
METHODSTwenty-six BALB/c mice were randomly divided into 3 groups: BMT group (group A, n = 10), BMT + vaccination group (group B, n = 10), control group (group C, n = 6). (BALB/c × C57BL/6) F1 mice [CB6F1, H-2K(b/d)] were used as donors. BALB/c mice of group C were only inoculated with Renca cell (2.6 × 10(6)). Mice of group A and B were conditioned with 8 Gy irradiation, followed by infusion by bone marrow cell of CB6F1 mice on day 1, then inoculated with Renca cell (2.6 × 10(6)) on day 8. All mice of group B were immunized subcutaneous on the back with 5 × 10(5) irradiated Renca tumor cells on day 9 and day 16. All mice of group C were inoculated with Renca cell (2.6 × 10(6)) on day 8. In group A and B, all mice were analyzed by fluorescence activated cell sorter (FACS) on day 14, and 28 day after BMT. Mice were killed on day 32 after inoculation with tumor cell and collected blood sample. All tumors were taken out to be weighed and then fixed in 10% buffered formalin, embedded in paraffin, and cut into 5 µm slices. The slices were stained with HE and examined by TdT mediated-dUTP nick end labeling (TUNEL). Liver, skin, intestine, and spleen were biopsied for histopathological examination.
RESULTSThe results of chimera showed that engraftments of group A, B were full donor chimerism, and the chimerism of those remained above 90% and preserved even after 28 days. The tumor weight, tumor volume increment in the group B was lower than group A and C (P < 0.05). The tumor suppressing rates of the group A and B were 54%, 60% respectively. The area ratio of tumor necrosis and apoptosis index (AI) of the tumor in the group B were higher than group A and C (P < 0.05). Graft-versus-host disease was not observed in each group.
CONCLUSIONThe mechanism of GVT after haploidentical allogeneic bone marrow transplantation with tumor vaccination may be the promotion of tumor necrosis and apoptosis.
