SIPULEUCEL-T CONSISTS OF AUTOLOGOUS PERIPHERAL BLOOD MONONUCLEAR CELLS, INCLUDING ANTIGEN PRESENTING CELLS (APCS), THAT HAVE BEEN ACTIVATED DURING A DEFINED CULTURE PERIOD WITH A RECOMBINANT HUMAN PROTEIN, PAP-GM-CSF, CONSISTING OF PROSTATIC ACID PHOSPHATASE (PAP), AN ANTIGEN EXPRESSED IN PROSTATE CANCER TISSUE, LINKED TO GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF), AN IMMUNE CELL ACTIVATOR. THE ACTIVE COMPONENTS OF SIPULEUCEL-T ARE AUTOLOGOUS APCS AND PAP-GM-CSF. DURING CULTURE, THE RECOMBINANT ANTIGEN CAN BIND TO AND BE PROCESSED BY APCS INTO SMALLER PROTEIN FRAGMENTS. THE RECOMBINANT ANTIGEN IS DESIGNED TO TARGET APCS, AND MAY HELP DIRECT THE IMMUNE RESPONSE TO PAP. MINIMAL RESIDUAL LEVELS OF THE INTACT PAP-GM-CSF ARE DETECTABLE IN THE FINAL SIPULEUCEL-T PRODUCT. THE CELLULAR COMPOSITION OF SIPULEUCEL-T IS DEPENDENT ON THE COMPOSITION OF CELLS OBTAINED FROM THE PATIENT'S LEUKAPHERESIS. IN ADDITION TO APCS, THE FINAL PRODUCT CONTAINS T CELLS, B CELLS, NATURAL KILLER (NK) CELLS, AND OTHER CELLS. THE NUMBER OF CELLS PRESENT AND THE CELLULAR COMPOSITION OF EACH SIPULEUCEL-T DOSE WILL VARY. EACH DOSE OF SIPULEUCEL-T CONTAINS A MINIMUM OF 50 MILLION AUTOLOGOUS CD54+ CELLS ACTIVATED WITH PAP-GM-CSF, SUSPENDED IN 250 ML OF LACTATED RINGER'S INJECTION.
THE POTENCY OF SIPULEUCEL-T IS IN PART DETERMINED BY MEASURING THE INCREASED EXPRESSION OF THE CD54 MOLECULE, ALSO KNOWN AS ICAM-1, ON THE SURFACE OF APCS AFTER CULTURE WITH PAP-GM-CSF. CD54 IS A CELL SURFACE MOLECULE THAT PLAYS A ROLE IN THE IMMUNOLOGIC INTERACTIONS BETWEEN APCS AND T CELLS, AND IS CONSIDERED A MARKER OF IMMUNE CELL ACTIVATION.