Differential Effects of a Murine and Chimeric Mouse/human Anti-interleukin-2 Receptor Antibody on Human T-cell Proliferation

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 1992 Jul 1

PMID 1526654

Authors

B Rose

A Gillespie

D Wunderlich

K Kelley

J Dzuiba

D Shedd

K Cahill

B Zerler

Affiliations

Soon will be listed here.

Abstract

The preference for interleukin-2 receptor (IL-2R) expression on activated, compared with resting T lymphocytes makes the IL-2R a promising target for selective immunosuppressive therapy. To increase the potential therapeutic effectiveness of anti-IL-2R monoclonals, a chimeric mouse/human variant was constructed from Ig genes isolated from a murine anti-human IL-2R hybridoma cell line, designated AHT54. AHT54 binds to the same or spatially related epitope as IL-2 on the p55 protein that constitutes the low- and high-affinity forms of IL-2R. Although the murine and chimeric AHT54 antibodies inhibited cell-surface binding of IL-2 to the same extent, the chimeric antibodies containing a human IgG1 constant region had substantially more anti-proliferative activity than their murine IgG1 counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in peripheral blood mononuclear cells (PBMC).

References

Smith K, Favata M, Oroszlan S . Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics. J Immunol. 1983; 131(4):1808-15. View

Southern P, Berg P . Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982; 1(4):327-41. View

Mulligan R, Berg P . Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981; 78(4):2072-6. PMC: 319285. DOI: 10.1073/pnas.78.4.2072. View

Honjo T, Obata M, Kataoka T, Kawakami T, Takahashi N, Mano Y . Cloning and complete nucleotide sequence of mouse immunoglobulin gamma 1 chain gene. Cell. 1979; 18(2):559-68. DOI: 10.1016/0092-8674(79)90072-2. View

Pirofski L, Casadevall A, Rodriguez L, Zuckier L, Scharff M . Current state of the hybridoma technology. J Clin Immunol. 1990; 10(6 Suppl):5S-12S; discussion 12S-14S. DOI: 10.1007/BF00918686. View

Junghans R, Waldmann T, Landolfi N, Avdalovic N, SCHNEIDER W, Queen C . Anti-Tac-H, a humanized antibody to the interleukin 2 receptor with new features for immunotherapy in malignant and immune disorders. Cancer Res. 1990; 50(5):1495-502. View

Kirkman R, Shapiro M, Carpenter C, Milford E, Ramos E, Tilney N . Early experience with anti-Tac in clinical renal transplantation. Transplant Proc. 1989; 21(1 Pt 2):1766-8. View

Waldmann T, Goldman C, Bongiovanni K, Sharrow S, Davey M, Cease K . Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2. Blood. 1988; 72(5):1805-16. View

Liu A, Robinson R, Murray Jr E, Ledbetter J, Hellstrom I, Hellstrom K . Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity. J Immunol. 1987; 139(10):3521-6. View

10.

Smith K . The interleukin 2 receptor. Adv Immunol. 1988; 42:165-79. DOI: 10.1016/s0065-2776(08)60844-5. View

11.

Khazaeli M, Saleh M, Wheeler R, Huster W, HOLDEN H, Carrano R . Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response. J Natl Cancer Inst. 1988; 80(12):937-42. DOI: 10.1093/jnci/80.12.937. View

12.

Morrison S . Transfectomas provide novel chimeric antibodies. Science. 1985; 229(4719):1202-7. DOI: 10.1126/science.3929380. View

13.

Ellison J, Berson B, HOOD L . The nucleotide sequence of a human immunoglobulin C gamma1 gene. Nucleic Acids Res. 1982; 10(13):4071-9. PMC: 320779. DOI: 10.1093/nar/10.13.4071. View

14.

Cantrell D, Smith K . The interleukin-2 T-cell system: a new cell growth model. Science. 1984; 224(4655):1312-6. DOI: 10.1126/science.6427923. View

15.

Leonard W, Depper J, Uchiyama T, Smith K, Waldmann T, Greene W . A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982; 300(5889):267-9. DOI: 10.1038/300267a0. View

16.

Rose B, Gillespie A, Wunderlich D, Barbosa J, Cahill K, Dzuiba J . A chimeric mouse/human anti-IL-2 receptor antibody with enhanced biological activities. Mol Immunol. 1992; 29(1):131-44. DOI: 10.1016/0161-5890(92)90164-s. View

17.

Kirkman R, Shapiro M, Carpenter C, McKay D, Milford E, Ramos E . A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation. Transplantation. 1991; 51(1):107-13. DOI: 10.1097/00007890-199101000-00016. View

18.

Soulillou J, Cantarovich D, Le Mauff B, Giral M, Robillard N, Hourmant M . Randomized controlled trial of a monoclonal antibody against the interleukin-2 receptor (33B3.1) as compared with rabbit antithymocyte globulin for prophylaxis against rejection of renal allografts. N Engl J Med. 1990; 322(17):1175-82. DOI: 10.1056/NEJM199004263221702. View

19.

Wijdenes J, Beliard R, Muot S, Herve P, Peters A . A semi-pharmaceutical approach for the preparation of an anti-IL2 receptor monoclonal antibody in the treatment of acute GvHD in a multicentric study. Dev Biol Stand. 1990; 71:103-11. View

20.

Osawa H, DIAMANTSTEIN T . Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107. Immunol Lett. 1989; 20(3):205-12. DOI: 10.1016/0165-2478(89)90081-3. View