AN ANTI-IL-2 ANTIBODY INCREASES SERUM HALFLIFE AND IMPROVES ANTITUMOREFFICACY OF HUMAN RECOMBINANT INTERLEUKIN-2

We examined the ability of anti-human recombinant interleukin-2 (hu rI L-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rI L-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v .) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (2 22 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of no n-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio re duced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated contr ols. Although similar treatment with hu rIL-2 alone reduced tumor grow th rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does no t have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 ant ibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts im mune response against tumor.