DNA immunization targeting carcinoembryonic antigen in colorectal cancer patients

Active specific immunotherapy targeting carcinoembryonic antigen (CEA) may induce antigen-specific humoral and cellular responses in cancer patients. Plasmid DNA, encoding tumor antigens, represents a novel approach of delivering conformational antigens. Here we report immune data of an explorative study using CEA66-DNA (non-glycosylated cytoplasmic CEA) and tetwtCEA-DNA (wild type glycosylated and secreted CEA) for immunization in combination with cyclophosphamide and GM-CSF in the adjuvant setting of radically operated colorectal cancer (CRC). 10 patients received intradermal (id) or intramuscular (im) CEA66-DNA delivered by needle-free Biojector at weeks 0, 2, 6 (part 1). 10 patients received tetwtCEADNA id by needle injection and electroporation at weeks 0 and 12 (part 2). In part 3, 6 patients were primed with CEA66-DNA and boosted with tetwtCEA-DNA. A significant increase of CD4 + effector memory, CD8 + effector and CD8 + effector memory T cells was seen in part 1. An immune response against CEA atleast one time point was noted in 15/20 (75%) patients in parts 1 and 2 together. The frequency of patients mounting a CEA-specific cellular immune responses was significantly higher in part 1 (100%) than in part 2 (50%) (p=0.03). In part 3, 5/6 (83%) patients showed a CEA-specific immune response after a prime-boost protocol. The higher CEA-specific T cell responses seen in part 1, may indicate reduced immunological tolerance induced by the non-glycosylated intracellularly produced CEA66-DNA immunogen. Humoral responses determined by ELISA were low. Further studies are warranted to optimize vaccination schedules to induce both cellular and humoral anti-CEA responses of clinical significance. Clinical trials.gov.identification number (parts 2/3) is NCT01064375.