Gong J, Chen L, Chen D, Kashiwaba M, Manome Y, Tanaka T, Kufe D
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Gene Ther. 1997 Oct;4(10):1023-8. doi: 10.1038/sj.gt.3300496.
Transduction of dendritic cells (DC) can result in presentation of tumor-associated antigens and induction of immunity against undefined epitopes. The present studies demonstrate adenovirus (Ad)-mediated transduction of the beta-galactosidase gene in mouse DC. Similar transductions have been obtained with the gene encoding the DF3/MUC1 tumor-associated antigen. We show that the Ad-transduced DC are functional in primary allogeneic mixed lymphocyte reactions. Mice immunized with Ad-transduced DC develop cytotoxic T lymphocytes that are specific for the beta-galactosidase or DF3/MUC1 antigens. The results also demonstrate that Ad MUC1-transduced DC induce a specific response which inhibits the growth of DF3/MUC1-positive tumors. These findings support the usefulness of Ad-transduced DC for in vivo immunization against tumor-associated antigens.
树突状细胞(DC)的转导可导致肿瘤相关抗原的呈递以及针对未明确表位的免疫诱导。本研究证明了腺病毒(Ad)介导的β-半乳糖苷酶基因在小鼠DC中的转导。用编码DF3/MUC1肿瘤相关抗原的基因也获得了类似的转导。我们表明,Ad转导的DC在原发性同种异体混合淋巴细胞反应中具有功能。用Ad转导的DC免疫的小鼠产生了对β-半乳糖苷酶或DF3/MUC1抗原特异的细胞毒性T淋巴细胞。结果还表明,Ad MUC1转导的DC诱导了一种特异性反应,该反应抑制了DF3/MUC1阳性肿瘤的生长。这些发现支持了Ad转导的DC用于体内针对肿瘤相关抗原免疫的有效性。