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PA2024-derived peptides presented by MHC on antigen-presenting cells (APCs) represent the functional antigenic component of the immunotherapy Sipuleucel-T [1, 3]. PA2024 is a recombinant fusion protein comprising human prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) [1, 3]. In the manufacturing of Sipuleucel-T, autologous APCs are incubated with PA2024, allowing the GM-CSF portion to direct the protein to APCs for uptake and processing [1, 2]. The PAP component is subsequently cleaved into peptides and loaded onto MHC Class I and II molecules for presentation to the patient's immune system [1, 2]. This presentation triggers the activation of PAP-specific T cells, which are then capable of recognizing and lysing prostate cancer cells that express the PAP antigen [2, 4]. This approach leverages the body's cellular immune system to target a specific tumor-associated antigen in metastatic castration-resistant prostate cancer [1, 3].
Activation of antigen-specific T cells through the presentation of tumor-associated antigens by dendritic cells.
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