A pilot clinical study with a therapeutic vaccine based on hydroxyapatite ceramic particles and self-antigens in cancer patients

CIOCCA D. R.; FRAYSSINET P.; CUELLO CARRIÓN F. D.

Berlin, Alemania

Simposio; IIIrd International Symposium on Heat Shock Proteins in Biology and Medicine; 2006

Cell Stress Society International

In the present study we have generated a therapeutic vaccine using self-antigens obtained from the tumor of the patient (autologous). The novel approach involved: a) the purification of the tumor antigens using column chromatography with hydroxyapatite (HA), b) the use of the HA as a medium to attract professional antigen presenting cells (APCs) to the injection site, and c) the use of HA as a vectar to present in vivo the tumor antigens and adjuvants to the patients APCs (the vaccine was composed of at least two heat shock proteins with chaperoned peptides, unidentified proteins from the cell membrane systern, and HA particles). When the HA particles were administered under the skin of rats, the larger particles attracted macrophages, the HA was biocompatible and totally degradable by the macrophages (at the 7th day). In the patients (n = 20) the vaccine toxicity was very low, causing only minor and tolerable local inflammatory signs (erythema, papule, or local pain), only one patient that received the larger doses (0.7 mL) presented a mild suffocation, none of the patients showed systemic manifestations of toxicity attributed to the vaccine or autoimmune diseases. The vaccine produced stable disease in 35% of the patients, including those with renal carcinoma (n = 2), breast carcinoma (n = 2), and astrocytoma (n = 3). The activation of a T cell response was shown in the comparative immunohistochemical study performed in the pre- and post-vaccine biopsy taken from a patient with inflammatory breast carcinoma. The most encouraging results were seen in patients with recurrent disease, four patients in these conditions (20%) are disease free following the vaccine administration, among them are those with recurrent melanoma (n = 1), astrocytoma (n = 2) and parotid carcinoma (n = 1). These results suggest that the vaccine is working mainly in patients where the tumor is still growing at the primary site and where the tumor mass has been decreased by surgery.