Abstract
The topic is how to achieve long-term protective anti-tumor immunity by anti-cancer vaccination and what are its mechanisms. Cancer vaccines should instruct the immune system regarding relevant cancer targets and contain signals for innate immunity activation. Of central importance is T-cell mediated immunity and thus a detailed understanding of cognate interactions between tumor antigen (TA)-specific T cells and TA-presenting dendritic cells. Microbes and their associated molecular patterns initiate early inflammatory defense reactions that can contribute to the activation of antigen-presenting cells (APCs) and to costimulation of T cells. The concommitant stimulation of naive TA-specific CD4+ and CD8+ T cells with TAs and costimulatory signals occurs in T-APC clusters that generate effectors, such as cytotoxic T lymphocytes and T cell mediated immunological memory. Information about how such memory can be maintained over long times is updated. The role that the bone marrow with its specialized niches plays for the survival of memory T cells is emphasized. Examples are presented that demonstrate long-term protective anti-tumor immunity can be achieved by post-operative vaccination with autologous cancer vaccines that are modified by virus infection.
Highlights
Like the brain with its network of neurons, the immune system has the capacity to learn and develop memory
Further studies revealed that dendritic cell (DC) that were pulsed with viral oncolysates stimulated significantly higher memory T cells (MTCs) ELISPOT responses than DCs that were pulsed with tumor lysate without virus (NDV) infection
As tumor antigen (TA) as peptides that are associated with MHC molecules (pMHC) complexes are of intra-cellular origin, their cognate immune response should be guided by TA presentation via DCs that are polarized towards T helper 1 (Th1) and cytotoxic T lymphocytes (CTLs) responses rather than by B cells and antibodies
Summary
Like the brain with its network of neurons, the immune system has the capacity to learn and develop memory Both phenomena are prerequisites for effective vaccination and long-term protective immunity. There are three participants in the molecular recognition of antigen by T cells: an antigenic fragment (peptide) that forms a complex with a presenter molecule (major histocompatibility complex (MHC) protein), and this complex is recognized by a recognition molecule, the antigen-specific T cell receptor (TCR) [1]. This review deals with cancer vaccines that are modified by infection with a natural attenuated oncolytic virus (OV). This relatively simple procedure requires high quality (GMP). Virus-based cancer vaccines involving genetic engineering [3,4] is a different concept and it will not be discussed here
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