Overview of studies

Cancer vaccines employing dendritic cells (DC) in their capacity as antigen-presenting cells (APC) have been tolerated well and have shown some efficacy in clinical studies. Interleukin (IL) -12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response. The Activartis technology uses a proprietary concept based on activation of tumour antigen charged DCs by exposure to a microbial danger signal (lipopolysaccharide, LPS) in the presence of Interferon (IFN) ?.

The general conclusion from our early clinical studies suggest that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in cancer patients. The treatment of patients with several different neoplastic diseases indicates that the concept of using tumour antigens derived from the patient basically enables the treatment of every cancer.

Orthopaedic cancer

Tumour lysate charged DCs were exposed to LPS/IFN-? for 6 hours and frozen. Extensive quality control assured that all specifications for clinical application were met. Fifteen patients suffering from multifocal metastasised sarcoma that had exhausted conventional multi-modal therapy were treated with the DC cancer vaccine. No adverse events were reported for any patient. The median progression free survival for all patients was 6.5 months; median overall survival for all patients was 23.3 months. To date, 3 of 15 patients are still alive at 30, 32, and 35 months. We were able to detect helper as well as cytotoxic T-cell reactivity in 5 of 6 studied patients. The delayed-type hypersensitivity (DTH) test was positive in 6 out of 6 patients against the tracer antigen KLH; and in 5 out of 6 patients against the tumour antigens.

Paediatric cancer

We applied tumour cell lysate plus keyhole limpet haemocyanin (KLH)- loaded and 48 hours LPS/IFN-? stimulated fully mature DCs, which do not release IL-12, subcutaneously to eight patients, and maximally 6 hours stimulated semi-mature (sm) DCs, which are potent producers of IL-12, subcutaneously (n=6) or intra-nodally (n=8) as a cancer vaccine to patients suffering from advanced solid paediatric malignancies. No serious adverse events were observed following the application of IL-12-releasing smDCs. Following the immunisation, the majority of patients responded positively to KLH in a delayed-type hypersensitivity (DTH) test. In addition, three of six intra-nodally treated patients responded to the tumour Ag in the DTH test.

Urologic cancer

Dendritic cells (DC) for cancer immune therapy are charged with tumour antigens derived from two sources: synthetic or recombinant shared tumour antigens, or surgically obtained whole tumour antigens from each patient. Synthetic antigens do not require surgery, whereas whole tumour protein covers the entire antigenic spectrum. We treated a series of 9 prostate cancer patients with DCs charged with recombinant PSA protein, and a series of 20 patients suffering from renal cell carcinoma using whole tumour cell protein. All cancer vaccines were tolerated well. In vitro analyses revealed that, in treated prostate cancer patients, no specific immune response against PSA was detected. In contrast, using whole tumour protein resulted in specific immune responses in a subset of patients. We conclude that using whole tumour protein to manufacture a DC cancer vaccine that is tailored for the individual patient has advantages over the use of synthetic shared tumour antigens.