A combination of interleukin-2 and 60 nm cationic supramolecular biovectors for the treatment of established tumours by subcutaneous or intranasal administration.
The Supramolecular Biovector (SMBV) KY is a drug delivery nanocarrier which consists of a discretely sized, ionically charged, cross-linked polysaccharide core surrounded by a lipid membrane. We used the non-immunogenic spontaneous mammary adenocarcinoma TS/A tumour to test the efficacy on tumour growth of low (10(4) IU) or ultra-low (10(3) IU) doses of interleukin-2 (IL-2) adsorbed to these 60 nm cationic synthetic particles. In comparison with the progressive growth of TS/A cells in syngeneic mice, KY/IL-2 particles coinjected with TS/A cells or administered at a distance from the tumour, inhibited tumour growth while free IL-2, even at 10-100 times the dose used in the KY/IL-2 formulations, had no effect. Studies performed on implanted tumours (treatment at day 6 (D6)) showed that KY/IL-2 administered subcutaneously (s.c.) at five sites distant from the tumour (10(3) IL-2 IU per site) induced rejection of the implanted tumours. Six out of 10 mice were cured while the other four had residual tumours only. In the same experiment, free IL-2 induced only tumoral growth reduction. Protection induced by KY/IL-2 administered s.c. at five sites involved recruitment of a CD8(+) T cell response since nu/nu mice and CD8-depleted mice did not reject the tumours. Mice cured were protected significantly to completely against a rechallenge with TS/A tumour cells, and a systemic tumour-specific CTL activity was induced. Finally, we showed that repeated intranasal (i.n.) administration of KY/IL-2 (low-dose) also led to complete regression of pre-established tumours and partial protection from tumour rechallenge. We therefore suggest that, in contrast to free IL-2, a KY/IL-2 formulation could be used as a systemic immunostimulant leading to the eradication of non-immunogenic, established tumours.
El mir
S
S
Laboratoire d'Immunologie des Tumeurs, Faculté de Pharmacie, 5, rue J.B. Clément, 92296, Chatenay-Malabry, France.
Casanova
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A
Betbeder
D
D
Triebel
F
F
D000230:Adenocarcinoma / Q000188:drug therapy*; D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage*; D008055:Lipids; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011134:Polysaccharides
D004337:Drug Carriers; D007376:Interleukin-2; D008055:Lipids; D011134:Polysaccharides