Antitumor effect of lung cancer vaccine with umbilical blood dendritic cells in reconstituted SCID mice.
Dendritic cells (DCs) are important cells in initiating an immune response. A generation of functional DCs has potential clinical use in treating cancer. However, the source of DCs and patient immunodeficiency with cancer have been hindrances in clinical therapy. We generated DCs from human umbilical cord blood mononuclear cells (UBMCs) with recombinant human granulocyte-macrophage colony stimulating factor, recombinant human interleukin-4, and recombinant human tumor necrosis factor-alpha. The mature DC-A549 lung cancer vaccine (AgL-DC) was prepared through loading A549 lysate, treating with lipopolysaccharide (LPS) and positive selecting with CD83 magnetic beads. AgL-DC can secrete interleukin (IL)-12 and IL-1. Further in vitro analysis showed that AgL-DC notably induced human UBMC lymphocyte proliferation (p < 0.01) by 3-(4,5-dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, increased the cytotoxic T-lymphocyte (CTL) activity of UBMC lymphocytes against A549 cells (p < 0.05, at effector cells:target cells ratios of 50:1 and 100:1) by lactate dehydrogenase (LDH) cytotoxic assay, and improved production of IL-6 and tumor necrosis factor-beta (p < 0.01, p < 0.05) by enzyme-linked immunosorbent assay. Subsequently, the reconstitute immunity model in severe combined immunodeficiencies (SCID) mice has been established using human UBMC transplantation, and similar trends to results of UBMC in vitro experiments have been shown in lymphocyte proliferation, CTL activity, and IL-6 and tumor necrosis factor-beta secretion levels in these models. AgL-DC also significantly (p < 0.01) increased the antitumor effect in vivo. The tumor infiltrating immunocytes were positively expressed human CD83 and CD3 molecules, and they were negatively expressed in tumor tissue treated with control. These results have demonstrated that umbilical cord DCs are a useful source of vaccine cells for augmenting CTL-mediated cytotoxicity and have potential usefulness in cellular therapy for human cancer in a new vaccination strategy.
Lin
Ping
P
Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, People's Republic of China.
Lu
Yan-Rong
YR
Zhang
Jie
J
Wei
Yu-Quan
YQ
Wang
Xiu-Jie
XJ
Li
Sheng-Fu
SF
Wang
Qi
Q
Xiong
Zhu-Juan
ZJ
Ning
Qi-Zhi
QZ
Lei
Song
S
Mao
Yong-Qiu
YQ
Cheng
Jing-Qiu
JQ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D007107:Immune System; D007136:Immunoglobulins / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D014471:Umbilical Veins / Q000166:cytology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D000970:Antineoplastic Agents; D017252:CD3 Complex; D007136:Immunoglobulins; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen