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 (TM)) KY is a drug delivery nanocarrier which consists of a discretely sized, ionically charged, cross-linked polys accharide core surrounded by a lipid membrane. We used the non-immunogenic spontaneous mammary adenocarcinoma TS/A tumour to test the efficacy on tumo ur 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 partic les coinjected with TS/A cells or administered at a distance from the tumou r, inhibited tumour growth while free IL-2, even at 10-100 times the dose u sed in the KY/IL-2 formulations, had no effect. Studies performed on implan ted tumours (treatment at day 6 (D6)) showed that KY/IL-2 administered subc utaneously (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 c ured 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 ce ll response since nu/nu mice and CD8-depleted mice did not reject the rumou rs. Mice cured were protected significantly to completely against a rechall enge with TS/A tumour cells, and a systemic tumour-specific CTL activity wa s induced. Finally, we showed that repeated intranasal (i.n.) administratio n of KY/IL-2 (low-dose) also led to complete regression of pre-established tumours and partial protection from tumour rechallenge. We therefore sugges t 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, est ablished tumours. (C) 2001 Elsevier Science Ltd. All rights reserved.