A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic particles and self-antigens in cancer patients.
We describe an approach to produce an autologous therapeutic antitumor vaccine using hydroxyapatite (HA) for vaccinating cancer patients. The novel approach involved (1) the purification of part of the self-tumor antigens/ adjuvants using column chromatography with HA, (2) the employ of HA as a medium to attract antigen-presenting cells (APCs) to the vaccination site, and (3) the use of HA as a vector to present in vivo the tumor antigens and adjuvants to the patient's APCs. The vaccine was prepared using and combining HA particles, with at least 3 heat shock proteins (gp96 was one of them possibly with chaperoned proteins/peptides as shown in the slot blots) and with proteins from the cell membrane system (including Hsp70, Hsp27, and membrane proteins). The timing of HA degradation was tested in rats; the HA particles administered under the skin attracted macrophages and were degraded into smaller particles, and they were totally phagocytized within 1 week. In patients (n = 20), the vaccine was then administered weekly and showed very low toxicity, causing minor and tolerable local inflammation (erythema, papule, or local pain); only 1 patient who received a larger dose presented hot flashes, and there were no systemic manifestations of toxicity or autoimmune diseases attributed to the vaccine. Our study suggests that this therapeutic vaccine has shown some efficacy producing a positive response in certain patients. Stable disease was noted in 25% of the patients (renal carcinoma, breast carcinoma, and astrocytoma), and a partial response was noted in 15% of the patients (breast carcinoma and astrocytoma). The most encouraging results were seen in patients with recurrent disease; 4 patients in these conditions (20%) are disease free following the vaccine administration. However, we do not want to overstate the clinical efficacy in this small number of patients. The therapeutic vaccine tested in our study is working by activating the T-cell response as was shown in the comparative histological and immunohistochemical study performed in the pre- and postvaccine biopsy taken from a patient with inflammatory breast carcinoma. However, we cannot ruled out that the vaccine could also be producing an antibody(ies)-mediated response. In conclusion, this therapeutic vaccine based on HA ceramic particles and self-antigens can be safely administered and is showing some encouraging clinical results in cancer patients.
Ciocca
Daniel R
DR
Argentine Foundation for Cancer Research, Sargento Cabral 706, 5500 Mendoza, Argentina. dciocca@lab.cricyt.edu.ar
Frayssinet
Patrick
P
Cuello-Carrión
F Darío
FD
D000328:Adult; D000368:Aged; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000138:chemical synthesis / Q000276:immunology* / Q000627:therapeutic use*; D002516:Ceramics; D017886:Durapatite / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology / Q000473:pathology
D001324:Autoantigens; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D017886:Durapatite