Therapeutic effect of intratumoral administration of DCs with conditional expression of combination of different cytokines.
In this study, we tested the effect of intratumoral administration of dendritic cells (DCs) with inducible expression of different cytokines, using the novel Rheoswitch Therapeutic System on the experimental models of renal cell cancer (RENCA) and MethA sarcoma. Intratumoral injection of DCs, engineered to express IL-12, IL-21, or IFN-α, showed potent therapeutic effect against established tumor. This effect was associated with the induction of potent tumor antigen-specific CD8+ T-cell responses, as well as the infiltration of tumors with CD4+ and CD8+ T cells but not with the cytotoxic activity of DCs. Combination of i.t. administration of DCs, producing different cytokines, did not enhance the antitumor effect of therapy with single cytokine. These results indicate that RTS can be a potent tool for conditional topical cytokine delivery, in combination with DC administration. However, combination of different cytokines may not necessarily improve the outcome of treatment.
Department of Immunology, H. Lee Moffitt Cancer Center, MRC 2067, 12902 Magnolia Dr. Tampa, Tampa, FL 33647, USA.
Chun
C
Huang
Rupal
R
Ramakrishnan
Marko
M
Trkulja
Xiubao
X
Ren
Dmitry I
DI
Gabrilovich
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004195:Disease Models, Animal; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012509:Sarcoma / Q000628:therapy*; D012878:Skin Neoplasms / Q000628:therapy*; D019076:Transgenes / Q000235:genetics; D000098546:Interleukin-21
D000951:Antigens, Neoplasm; D016207:Cytokines; D016898:Interferon-alpha; D007378:Interleukins; D018664:Interleukin-12; D000098546:Interleukin-21