An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens

Abstract

Viral modification of dendritic cells (DCs) may deliver a "danger signal" critical to the hyporeactive DCs in cancer patients. Using three highly differentially expressed hepatoma tumor-associated antigens (TAAs): stem cell antigen-2 (Sca-2), glycoprotein 38 (GP38) and cellular retinoic acid binding protein 1 (RABP1), we explored the therapeutic potential of the DCs modified with lentiviral vectors (LVs). Preventive and therapeutic injection of the LV-TAA-DC vaccine into tumor-bearing mice elicited a strong anti-tumor response and extended survival, which was associated with tumorspecific interferon-γ and cytotoxic T cell responses. In vivo elimination of the LV-TAA-DCs by a co-expressed thymidine kinase suicide gene abrogated the therapeutic effect. The modification of DCs with LVs encoding multiple TAAs offers a great opportunity in cancer immunotherapy.

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

“…Therefore, vaccination with pMC-DCs expressing the entire tumor antigen may be more effective for inducing antigen-specific CTLs, which could elicit potent antitumor responses. Moreover, pMC-DCs expressing multiple tumor antigens may exert a higher therapeutic effect (39)(40)(41). In addition to manipulation of the tumor antigens, modification of pMCDCs through the transduction of immunostimulatory molecules (such as IL21) may improve the cellular immune responses (25,42).…”

Sequential allogeneic and autologous CAR-T–cell therapy to treat an immune-compromised leukemic patient

“…12,13 A new generation CAR, containing CD19-specific single-chain variable fragment fused with CD28-CD27-CD3z signaling domains and an inducible caspase 9 motif, was chemically synthesized and cloned into pTYF transducing vector behind a human EF1a promoter. [7][8][9] The final LV-CAR construct was extensively verified by functional analyses.…”

Induction of primary anti-HIV CD4 and CD8 T cell responses by dendritic cells transduced with self-inactivating lentiviral vectors

“…The SIN-LVs have been used to deliver cytokine, T cell costimulator and siRNA genes to modify DC immunity, and can effectively induce an anti-cancer immunity in vivo by overexpressing multiple highly differentiated cancer antigens in DCs (4,5). During LV gene transfer, the HIV Gag and Pol proteins in the vector particles may be processed in DCs through the MHC class II pathway or cross-presented via the MHC class I pathway (6,7).…”