Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary lymphoid-tissue chemokine (SLC/CCL21) is a CC chemokine that is constitutively expressed in various lymphoid tissues and binds to chemokine receptor CCR7 on mature dendritic cells (DCs) and distinct T-and B-cell sub-populations. In vivo, CCL21 regulates the encounters between DC and T cells and thus is a key regulator of adaptive immune responses. We asked whether CCL21 is able to augment immunogenicity of a DNA-based vaccine against Her2/neu in a Balb/c mouse model with syngeneic Her2/neu+ tumor cells (D2F2/E2). Mice were vaccinated intramuscularly with plasmid DNA (pDNA) on day 1 and boosted on day 15; tumor challenge was performed subcutaneously on day 25. Coexpression of CCL21 and Her-2/neu resulted in induction of a TH1-polarized immune response and substantial improvement of the protective effect of the DNA vaccine. Coexpression of tumor antigen pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) as adjuvants led to further improvement of protection by the vaccine (70% tumor-free mice on day 35 vs 40% with either adjuvant alone vs 5-10% with tumor antigen alone). Our results show that CCL21 is a potent adjuvant for DNA vaccination, particularly in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu/CCL21/GM-CSF) vaccine might be particularly promising in minimal residual Her2/neu+ breast cancer.
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PMID:CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model. 2199 31

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor-specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8+ T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8+ T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8+ T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8+ T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo.
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PMID:In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro. 2931 71