Can red blood cells prove to be a useful tool in tumor immunotherapy?

Autor: Françoise Horand, Yann Godfrin, Magali Cremel
Rok vydání: 2012
Předmět:
Zdroj: Immunotherapy. 4:871-873
ISSN: 1750-7448
1750-743X
DOI: 10.2217/imt.12.88
Popis: of migrating to the secondary lymphoid organs and of inducing an effective cytotoxic T‐cell response. In the second strategy, a variety of approaches have been explored to load and mature DCs directly in vivo such as generating TAAs linked to an antibody that recognizes cell surface recep‐ tors present only on DCs [9]. This approach overcomes the problem of DC migration to the lymph nodes that remains critical in the develop‐ ment of DC‐based vaccines using ex vivo load‐ ing. However, in this case, only limited numbers of TAAs can be processed by DCs and coadmin‐ istration of a maturation stimulus is required. In addition, cautions have to be applied regarding the possible expression of targeted receptor on other cell types, for example B or T cells. Taking into account all these difficulties of DC handling, innovative approaches to efficiently target DCs in situ are expected. Red blood cells (RBCs) are the most abun‐ dant cells in the blood, accounting for approxi‐ mately 40–45% of its volume. The cells develop in the bone marrow and circulate for approxi‐ mately 120 days in the bloodstream until senes‐ cence or damage. Unlike many other cells, RBCs have no nucleus and can easily change shape. At the end of their life, RBCs are removed from the blood circulation by erythrophagocytosis. Cells are naturally trapped by the reticuloen‐ dothelial system and are phagocytosed mainly by macrophages of the spleen, liver and bone marrow [10]. The potential of these cells as carriers of drugs has been identified for decades [11]. A large panel of molecules, including enzymes, peptides and proteins, can be entrapped into RBCs using a reversible hypotonic lysis process [12,13]. Thus, under hypotonic conditions, the erythrocytes swell and pores (~20 nm) appear Cancer immunotherapy aims to stimulate the patient’s immune system to kill or suppress the tumor. The discovery of tumor‐associated anti‐ gens (TAAs) has provided important advances in tumor immunology [1,2]. These molecules have been used to generate tumor‐specif ic immune responses combining both the humoral response and the generation of TAA‐specific cytotoxic T lymphocytes that infiltrate tumor tissues and are able to control tumor growth [3]. Induction of efficient cytotoxic T‐lymphocyte responses is the goal of most current vaccine strategies in tumor immunology [4]. Dendritic cells (DCs) are the only cells able to efficiently activate naive T cells and thus represent the crucial sentinel cells of the adaptive immune system. Presentation of TAA‐derived peptides by these cells constitutes the first step for tumor immunization. Thus, efficient and targeted delivery of several TAAs to DCs in vivo rep‐ resents a major step towards the development of more effective tumor vaccines. Several can‐ cer immunotherapeutic strategies targeting DCs have been developed [5,6], based either on in vitro DC manipulation or in vivo stimulation. In the first strategy, DCs are obtained from the patient [7]. Once harvested, cells are pulsed with TAAs or transfected with a viral vector or plasmid encoded to express TAAs. After activation with an immune stimulator, DCs are injected back into the patient and will pres‐ ent the antigens to effector lymphocytes (CD4 and CD8 T cells) [8]. This process has several drawbacks (it is laborious, expensive, time consuming and the number of activated DCs is limited). Moreover, the use of DCs ex vivo raised a certain number of issues on the state of maturation of the DC, the number of cells to be injected, the route, the site and the fre‐ quency of injection for producing DCs capable
Databáze: OpenAIRE
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