Dendritic-Cell-Based Therapeutic Cancer Vaccines

Abstract

The past decade has seen tremendous developments in novel cancer therapies, through targeting of tumor cell-intrinsic pathways whose activity is linked to genetic alterations, as well as the targeting of tumor cell-extrinsic factors such as growth factors. Furthermore, immunotherapies are entering the clinic at an unprecedented speed following the demonstration that T cells can efficiently reject tumors and that their anti-tumor activity can be enhanced with antibodies against immune regulatory molecules (checkpoints blockade). Current immunotherapy strategies include monoclonal antibodies against tumor cells or immune regulatory molecules, cell-based therapies such as adoptive transfer of ex vivo activated T cells and natural killer (NK) cells, and cancer vaccines. Herein, we discuss the immunological basis for therapeutic cancer vaccines and how the current understanding of dendritic cell (DC) and T cell biology might enable development of next-generation curative therapies for patients with cancer.

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

“…Therefore, vaccine strategies have been developed with properties that mimic pathogen composition and immunological processing to generate stronger immune responses. 2 Co-delivery of antigen and adjuvant into the same APC has been shown to induce a stronger tumor-specific T cell response compared to delivery of antigen and adjuvant as a mixture. [3][4][5] Thereby, the antigen is processed in the APC and presented on the major-histocompatibility complex (MHC) molecules for T cell binding while the adjuvant activates the APC to express co-stimulatory molecules for full CTL and Th cell activation.…”

The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy

“…Its unique capacity to present antigens and initiate antigen-specific T cell responses, makes the DC an interesting target in cancer immunotherapy. By modifying DCs to present tumor-derived antigens to T cells, the patient's own immune system can be harnessed in the battle against the tumor [2]. For such a DC-based vaccine to be effective, two major requirements need to be satisfied.…”

Problems of Cancer Treatment. Part 2. Treatment Based on Modification of Anticancer Immunological Responses in Therapy

“…The question also arises whether presence of lymphocyte infiltrates in a tumour reflects the initial condition of a patient or (and to which extent) it has resulted from treatment (neoadjuvant chemotherapy). Results of studies on cells propagating the tumour seem to indicate the new sensible direction of studies: a pronounced expression of PD-L1 was demonstrated on cells of head and neck cancers; possibly they can be significantly responsible for mobilization of the mechanisms which reduce cytotoxicity of lymphocytes T [54]. It should be remembered that PD-L1 becomes expressed not only on cancer cells but also on lymphoid and myeloid cells and the appropriate therapeutic conclusions can be drawn only when distinction is made between the populations.…”