Evaluation of particulate systems supporting tumor cell fractions in a preventive vaccination against intracranial rat glioma.
OBJECTIVE
Irradiated autologous tumor cells are commonly used as a source of antigens in antiglioma vaccinations to activate the immune system. As cell number is often a limiting factor in these cells' preparation, the aim of the present study was to find a means that can lower the amount of cells required. Among strategies currently developed, adjuvant particulate systems offer a promising means to improve the antitumor immune response. In this study, the authors were interested in evaluating the role of particulate systems containing biodegradable microspheres that carry tumor cell fractions on their surfaces in the induction of a protective immunity in the 9L/Fischer 344 rat glioma model. The efficiency of these particulate systems was compared to that of irradiated 9L cells.


METHODS
Particulate systems composed of poly(D,L-lactide-co-glycolide) (PLGA) microspheres that support 9L cell fractions on their surfaces (cell lysates or plasma membranes) or irradiated 9L cells alone were injected subcutaneously into the flanks of syngeneic Fischer 344 rats. Eighteen days later, the rats were intracranially injected with nonirradiated 9L cells. A study of survival in these animals and an analysis of the resulting immune response were then conducted. For the same amount of protein (50 microg) injected, irradiated 9L cells provided long-term survival in 30% of animals, whereas 9L plasma membranes adsorbed onto PLGA microspheres provided long-term survival in 10% of animals and cell lysates adsorbed onto microspheres provided long-term survival in 0%. Accordingly, particulate systems induced a lower T helper cell Type 1 (Th1) peripheral immune response than irradiated 9L cells. However, greater secretion of Th1 cytokines was observed when particulate systems were used than when cell fractions separated from microspheres were used, indicating the adjuvant property of these particulate systems.


CONCLUSIONS
Particulate systems have adjuvant properties but are still less efficient than irradiated whole tumor cells for vaccinations. Encapsulation of an activating molecule in the microsphere will be the next developmental step in the search for efficient antiglioma vaccinations.
Sapin
Anne
A
L'Institut National de la Santé et de la Recherche Médicale U 646, Angers, France.
Clavreul
Anne
A
Garcion
Emmanuel
E
Benoit
Jean-Pierre
JP
Menei
Philippe
P
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D001672:Biocompatible Materials; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D019496:Cancer Vaccines; D002458:Cell Fractionation; D002462:Cell Membrane / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D019344:Lactic Acid; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000648:ultrastructure
D000951:Antigens, Neoplasm; D001672:Biocompatible Materials; D019496:Cancer Vaccines; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid