Premium
Combination of γ‐irradiation and dendritic cell administration induces a potent antitumor response in tumor‐bearing mice: Approach to treatment of advanced stage cancer
Author(s) -
Nikitina Ekaterina Yu.,
Gabrilovich Dmitry I.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20011215)94:6<825::aid-ijc1545>3.0.co;2-5
Subject(s) - cd8 , mhc class i , dendritic cell , elispot , cancer research , antigen , t cell , antigen presentation , cytotoxic t cell , immune system , medicine , immunology , biology , biochemistry , in vitro
We investigated a new approach to the treatment of advanced stage cancer, a combination of apoptosis‐inducing therapy and dendritic cell (DC) administration. MethA sarcoma and C3 tumor containing defined tumor‐specific antigens in form of peptides' epitopes were selected as experimental mouse models. Sites of established subcutaneous tumors were γ‐irradiated with 10 Gy 3–5 times with 4–5 day interval. DCs generated from bone marrow of syngeneic mice were injected i.v. and s.c. after each irradiation. A large number of cell tracker‐labeled DCs accumulated at the site of the irradiated tumor after s.c. injections. This effect was not observed in non‐irradiated tumors. Almost all of these DCs bound GFP‐labeled MethA cells in tumor tissue. Interferon‐γ production by splenocytes in response to the tumor‐specific MHC class I matched peptides was determined by ELISPOT assays. The combination of γ‐irradiation and DC administration, but not each of the treatments alone resulted in a significant increase in T cell response to the specific, but not to the control peptides. An increased proportion of tumor peptide‐specific CD8 + ‐cells was found only in that group of mice using staining with tetramers. DCs with defective presentation of antigen via MHC class I or MHC class II pathways were unable to induce peptide‐specific T cell response. The combination of γ‐irradiation and DC administration but not each of the treatments alone resulted in a dramatic antitumor effect. A substantial proportion of mice completely rejected their tumors (80% in case of MethA sarcoma and 40% in case of C3 tumor). In the rest of the mice, tumor growth was notably suppressed or completely blocked. These data suggest that the combination of apoptosis‐inducing therapy and DC administration may be an attractive approach to the treatment of advanced cancer. © 2001 Wiley‐Liss, Inc.