Effectiveness of allogeneic CD3AK cells on transplanted human renal cell cancer in mice with severe combined immune deficiency.
OBJECTIVE
To assess the activity of allogeneic anti-CD3 antibody induced activated killer (CD3AK) cells on transplanted human renal cell cancer (RCC) in mice with severe combined immune deficiency (SCID), thus to provide theoretical and experimental support for clinical application of allogeneic CD3AK cells in the treatment of RCC.


METHODS
A culture system which can massively increase allogeneic CD3AK cells was constructed. CCK-8 method was used to detect lethal effect of allogeneic CD3AK cells on human OS-RC-2 renal cancer cell line. Then, tumor-bearing mice models were constructed. SCID mice were randomly divided into four groups: group A (caudal vein was injected with allogeneic CD3AK cells before tumor bearing), group B (the control group of group A: caudal vein was injected with PBS before tumor bearing), group C (caudal vein was injected with allogeneic CD3AK cells after tumor bearing) and group D (the control group of group C: caudal vein was injected with PBS after tumor bearing), and spleen parameters were calculated to observe any inhibitory effect of allogeneic CD3AK cells on the growth of renal cancer cells, as well as their effect on the immune system of mice.


RESULTS
Compared with the control groups B and D, spleen parameters of groups A and C increased significantly (p<0.05); compared with group C, spleen parameters of group A showed no obvious difference (p>0.05); compared with the control groups B and D, tumor weight of groups A and C decreased significantly and tumors grew slowly (p<0.05); the weight of mice in all groups increased while the weight of mice in the experimental groups increased less than the weight of mice in the control groups (p<0.05); compared with group C, tumor weight of group A reduced and grew slowly (p<0.05). Immunohistochemistry revealed that CD3+ cells showed positive expression in tumor tissues of mice in group C, while no positive expression was found in tumor tissues of mice in other groups.


CONCLUSIONS
Allogeneic CD3AK cells exerted lethal effect on OS-RC-2 cell line and significant inhibitory activity on the growth of transplanted cancer in mice with SCID. Also CD3AK cells expressed certain preventive effect on the development of implanted cancer in SCID mice; allogeneic CD3AK cells possessed antitumor activity and could enhance the immunologic functions of SCID mice with human renal cell-bearing cancer.
Department of Urology, Zhengzhou People's Hospital, Zhengzhou, Henan, China.
Lei
L
Ge
Zhongjie
Z
Shan
Qianhe
Q
Han
Nan
N
Zhang
Yang
Y
Zhao
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016513:Mice, SCID; D010641:Phenotype; D013997:Time Factors; D014184:Transplantation, Homologous; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D017252:CD3 Complex