Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Glycoprotein – e.g. – mucins – proteoglycans – etc.
Patent
1990-11-28
1994-02-22
Nucker, Christine M.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Glycoprotein, e.g., mucins, proteoglycans, etc.
530350, 530808, 530827, 530868, 424 88, C07K 900, A61K 3702
Patent
active
052888541
DESCRIPTION:
BRIEF SUMMARY
ch is substantially incapable of binding to Mac-1, but is substantially capable of binding to LFA-1.
The invention specifically includes those of the above-described ICAM-1 functional derivatives which comprises Domains 1, 2, 3 and 4 of ICAM-1, and especially such derivatives which contain a mutation in Domain 3 of ICAM-1. Particularly preferred mutations in Domain 3 are mutations in ICAM-1 residues 229-231, or 254-256 of ICAM-1.
The present invention also provides an ICAM-1 functional derivative, especially a soluble derivative, which is substantially incapable of binding to LFA-1, but is substantially capable of binding to Mac-1. Among such derivatives are those which lack Domain 1, of ICAM-1, and those which contain Domains 1, 2, 3, 4 and 5 of ICAM-1, but contain a mutation in Domains 1 or 2 of ICAM-1. Particularly preferred mutations are those in ICAM-1 residue(s) E34, Q58ED, or Q73 of Domain 1 of ICAM-1. Among preferred ICAM-1 functional derivatives which lack Domain 1 are those comprising Domains 3 and 4 of ICAM-1.
The invention also provides an ICAM-1 functional derivative which is substantially incapable of binding to Mac-1 and LFA-1, but is substantially capable of binding a human rhinovirus.
The invention also pertains to an ICAM-1 functional derivative lacking a glycosylation site, wherein the derivative is capable of enhanced binding ability to Mac-1. Most preferred for this purpose is the loss of a glycosylation site at ICAM-1 residue N269, N240 or N358 of ICAM-1.
The invention also provides an anti-inflammatory agent characterized in being capable of treating inflammation caused by a reaction of the non-specific defense system, but being substantially incapable of suppressing inflammation caused by a reaction of the specific defense system.
In particular, the invention provides an anti-inflammatory agent which is an ICAM-1 functional derivative, especially a soluble derivative, that is substantially incapable of binding to LFA-1, but is substantially capable of binding to Mac-1.
The invention also provides an anti-inflammatory agent characterized in being capable of treating inflammation caused by a reaction of the specific defense system, but being substantially incapable of suppressing inflammation caused by a reaction of the non-specific defense system.
In particular, the invention provides an anti-inflammatory agent which is an ICAM-1 functional derivative, especially a soluble derivative, that is substantially incapable of binding to Mac-1, but is substantially capable of binding to LFA-1.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 shows the adhesion of LFA-1 and Mac-1 COS cell transformants to purified ICAM-1.
FIG. 2 shows a dose response curve of ICAM-1+ L cell adhesion to purified Mac-1.
FIG. 3 shows an avidity comparison of ICAM-1+ L cells for purified Mac-1 and LFA-1.
FIG. 4 shows the temperature dependence of ICAM-1+ cell adhesion to purified Mac-1 and LFA-1.
FIG. 5 shows HUVEC adhesion to purified Mac-1.
FIG. 6 shows monoclonal antibody inhibition studies of ICAM-1+ L cell adhesion to purified Mac-1 and LFA-1.
FIG. 7 shows the binding of domain deletion mutants of ICAM-1 to LFA-1 and Mac-1. The data is the average of three independent experiments and the error bars represent standard deviations.
FIG. 8 shows the effect of the endoplasmic reticulum glucosidase inhibitor deoxymannojirimycin on adhesion of ICAM-1.sup.+ cells to Mac-1.
FIG. 9 shows the effect of side claim glycosylation on ICAM-1 L cell adhesion to purified Mac-1.
FIG. 10 shows the amino acid sequence of ICAM-1.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
I. Treatment of Inflammation
The present invention pertains to ICAM-1, Mac-1 and their "functional derivatives," and to antibodies (and antibody fragments) which are capable of binding to ICAM-1 and thereby affecting the ability of ICAM-1 to bind to Mac-1.
One aspect of the present invention relates to the discovery that ICAM-1 is capable of binding to Mac-1, and to the identification of the domains of ICAM-1 which are responsible for the molecule's ability to bin
REFERENCES:
Sanchez-Madrid, F. et al. J. Exp. Med. 158:1785-1803. Dec. 1983. "A human leukocyte . . . ".
Sanchez-Madrid, F. et al. J. Exp. Med. 158:586-602. Aug. 1983. "Mapping of antigenic . . . ".
Staunton, D. et al. Cell 52:925-933. Mar. 1988. "Primary Structure of ICAM-1 . . .".
Altieri, D. C. et al., J. Biol. Chem. 263:7007-7015 (1988).
Altieri, D. C. et al., J. Cell. Biol. 107:1893-1900 (1988).
Arnaout, M. A. et al., J. Clin. Invest. 74:1291-1300 (1984).
Arnaout, M. A., et al., J. Cell. Physiol. 137:305-309 (1988).
Anderson, D. C., et al., Ann. Rev. Med. 38:175-194 (1987).
Anderson, D. C. et al., J. Immunol. 137:15-27 (1986).
Beller, D. I., et al., J. Exper. Med. 156:1000-1009 (1982).
Bullock, W. D., et al., J. Exper. Med. 165:195-210 (1987).
Dana, N. et al., J. Immunol. 137:3259-3263 (1986).
Davignon, D., et al., J. Immunol. 127:590-595 (1981).
Davignon, D., et al., PNAS U.S.A. 78:4535-4539 (1981).
Detmers, P. A. et al., J. Cell. Biol. 105:1137-1145 (1987).
Dustin, M. L., et al., J. Cell. Biol. 107:321-331 (1988).
Hogg, N., et al., Eur. J. Immunol. 16:240-248 (1986).
Hynes, R. O., Cell 48:549-554 (1987).
Caligaris-Cappio, F., et al., Blood 66:1035-1042 (1985).
Keizer, G. D., et al., J. Immunol. 138:3130-3136 (1987).
Keizer, G. D., et al., Eur. J. Immunol. 17:1317-1322 (1987).
Kishimoto, T. K., et al., Cell 48:681-690 (1987).
Kishimoto, T. K., et al., Adv. Immunol. 46:149-182 (1989).
Krensky, A. M., et al., J. Immunol. 131:611-616 (1983).
Lanier, L. L., et al., Eur. J. Immunol. 15:713-718 (1985).
Lo., S. K., et al., J. Immunol. 143(10):3325-3329 (1989).
Lo, S. K., et al., J. Exp. Med. 169:1779-1793 (1989).
Luscinskas, F. W., et al., J. Immunol. 142(7):2257-2263 (1989).
Marlin, S. D., Cell 51:813-819 (1987).
Mentzer, S. J., et al., J. Cell. Physiol. 130:410-415 (1987).
Micklem, K. J., et al., Biochem. J. 231:233-236 (1985).
Miller, L. J., et al., J. Immunol. 138:2381-2383 (1987).
Miller, L. J., et al., J. Immunol. 137:2891-2900 (1986).
Miller, L. J., et al., J. Clin. Invest. 80:535-544 (1987).
Mosser, D. M., et al., J. Immunol. 135:2785-2789 (1985).
Rosen, H., et al., J. Exper. Med. 166:1685-1701 (1987).
Ruoslahti, E., et al., Science 238:491-497 (1987).
Sanchez-Madrid, F., et al., PNAS U.S.A. 79:7489-7493 (1982).
Sastre, L., et al., PNAS U.S.A. 83:5644-5648 (1986).
Schwarting, R., et al., Blood 65:974-983 (1985).
Simmons, D., et al., Nature 331:624-627 (1988).
Smith, C. W., et al., J. Clin. Invest. 83:2008-2017 (1989).
Springer, T. A., et al., Ann. Rev. Immunol. 5:223-252 (1987).
Springer, T. A., et al., Eur. J. Immunol. 9:301-306 (1979).
Springer, T. A., et al., Nature 314:540-542 (1985).
Springer, T. A., et al., Fed. Proc. 44:2660-2663 (1985).
Staunton, D. E., Nature 339:61-64 (1989).
Staunton, D. E., et al., Cell 61:243-254 (1990).
te Velde, A. A., et al., Immunology 61:261-267 (1987).
Todd, R. F., et al., Hem. Onc. Clinics N.A. 2:13-31 (1988).
Todd, R. F., et al., J
This invention was made in part with government support. The government has certain rights in this invention.
Diamond Michael S.
Springer Timothy A.
Staunton Donald E.
Center For Blood Research, Inc.
Cunningham T.
Nucker Christine M.
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