Sipuleucel-T is an autologous cellular immunotherapy designed to induce an immune response targeted against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers. Peripheral blood mononuclear cells collected from the patients are cultured with PAP-GM-CSF, a fusion protein consisting of PAP linked to granulocyte-macrophage colony-stimulating factor (GM-CSF) an immune cell activator. During ex vivo culture with PAP-GM-CSF, activated APCs (antigen presenting cells) take up and process the recombinant target antigen into peptides that are then presented to T cells. Product characterization shows that PAP and PAP-GM-CSF fusion protein-specific T cells are generated during treatment and are detected in the peripheral blood of patients after treatment with sipuleucel-T.
CD54 is an adhesion and costimulatory molecule essential in the formation of the immunological synapse between an APC and a T cell. The degree of CD54 upregulation correlates with overall survival in the randomised controlled clinical trials carried out with autologous peripheral blood mononuclear cells activated with PAP-GM-CSF (Sipuleucel-T) in metastatic castrate resistant prostate cancer. In clinical study D9902B (IMPACT), 237 out of the 512 patients randomized were evaluated for the development of humoral or cellular immune responses (T cell proliferation and gamma-interferon (γIFN) ELISPOT) to the target antigens at baseline, and at Weeks 6, 14, and 26. Antibody (IgM and IgG) responses against both PAP-GM-CSF and the PAP antigens were observed in the sipuleucel-T group through the follow up period. T cell proliferative and γIFN ELISPOT responses to PAP and PAP-GM-CSF were observed in cells collected from peripheral blood of patients through the follow-up period in the sipuleucel-T treatment group but not in controls. There was a correlation between cellular or antibody responses to PAP or PAP-GM-CSF in the sipuleucel-T group and improved survival. Neutralising antibody responses to GM-CSF were transient.
Sipuleucel-T is an autologous cellular therapy. Its nature is such that conventional studies on pharmacokinetics, absorption, distribution, metabolism, and elimination are not applicable.
Conventional toxicology, carcinogenicity, mutagenicity, and reproductive toxicity studies have not been performed.
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