Research Paper | Published:

Controlled Release of Interleukin-2 from Biodegradable Microspheres

Bio/Technologyvolume 8pages755758 (1990) | Download Citation

Subjects

Abstract

We have evaluated the use of biodegradable poly(DL-lactide-co-glycolide) microspheres for the controlled release of interleukin-2 (IL-2) and its modified forms: succinyl IL-2 (SIL-2) and polyethylene glycol-modified IL-2 (PEG IL-2). We show that a microsphere formulation can be prepared from PEG IL-2 using HSA as an excipient which, after an initial burst, releases 2–3% PEG IL-2 per day in a bioactive form continuously over a 20- to 30-day period.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Smith, K.A. 1984. Interleukin 2. Ann. Rev. Immunol. 2: 319–333.

  2. 2

    Rosenberg, S.A., Spiess, P., Lafreniere, R. 1986. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233: 1318–1321.

  3. 3

    Ettinghausen, S.E., Rosenberg, S.A. 1986. Immunotherapies of murine sarcomas using lymphokine activated killer cells: optimization of the schedule and route of administration of recombinant interleukin-2. Cancer Res. 46: 2784–2792.

  4. 4

    Cheevar, M.A., Thompson, J.A., Peace, D.J., Greenberg, P.D. 1986. Potential uses of interleukin-2 in cancer therapy. Immunobiol. 172: 365–382.

  5. 5

    Rosenberg, S.A., Mule, J.J., Spies, P.J., Reichert, C.M., Scwarz, S.L. 1985. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin-2 J. Exp. Med. 161: 1169–1188.

  6. 6

    Lotze, M.T., Frana, L.W., Sharrow, S.O., Robb, R.J., Rosenberg, S.A. 1985. In vivo administration of purified human interleukin-2. Half-life and immunologic effects of jurkat cell line-derived interleukin-2. J. Immunol. 134: 157–166.

  7. 7

    Cheever, M.A., Thompson, J.A., Kern, D.E., Greenberg, P.D. 1985. Interleukin 2 (IL-2) administration in vivo: influence of IL-2 route and timing on T cell growth. J. Immunol. 134: 3895–3900.

  8. 8

    Nunberg, J.H., Doyle, M.V., York, S.M., York, C.J. 1989. Interleukin-2 acts as an adjuvant to increase the potency of inactivated rabies virus vaccine. Proc. Natl. Acad. Sci. USA 86: 4240–4243.

  9. 9

    Donohue, J.D., Rosenberg, S.A. 1983. The fate of interleukin-2 after in vivo administration. J. Immunol. 130: 2203–2208.

  10. 10

    Nishimura, T., Togashi, Y., Goto, M., Yagi, H., Uchiyama, Y., Hashimoto, Y. 1986. Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2. Cancer Immunol. Immunother. 21: 12–18.

  11. 11

    Morikawa, K., Okada, F., Hosokawa, M., Kobayashi, H. 1987. Enhancement of therapeutic effects of recombinant interleukin-2 on a transplantable rat ribrosarcoma by the use of a sustained release vehicle, Pluronic gel. Cancer Res. 47: 37–41.

  12. 12

    Matsuoka, J., Sakagami, K., Shiozaki, S., Uchida, S., Fujiwara, T., Gohchi, A., Orita, K. 1988. Development of an interleukin-2 slow delivery system. Trans. Am. Soc. Artif. Intern. Organs. 34: 729–731.

  13. 13

    DeLoach, J.R., Andrews, K., Sheffield, C.L. 1988. Encapsulation of interleukin-2 in murine erythrocytes and subsequent deposition in mice receiving a subcutaneous injection. Biotechnol. Appl. Biochem. 10: 183–190.

  14. 14

    Cutright, D.E., Brady, J.M., Getter, L., Miller, R.A. 1976. USDC national technical information service report no. AD-AO25 988.

  15. 15

    Gilding, D.K., Reed, A.M. 1979. Biodegradable polymers for use in surgery-polyglycolic/polylactic acid homo- and copolymers:1. Polymer. 20: 1459–1464.

  16. 16

    Beck, L.R., Pope, V.Z., Flowers, Jr., C.E., Cowsar, D.R., Tice, T.R., Lewis, D.H., Dunn, R.L., Moore, A.B., Gilley, R.M. 1983. Poly(DL-lactide-co-glycolide)/northisterone microcapsules: an injectable biodegradable contraceptive. Biol. Reprod. 28: 186–195.

  17. 17

    Redding, T.W., Schally, A.V., Tice, T.R., Meyer, W.M. 1984. Long-acting delivery systems for peptides: inhibition of rat prostrate tumors by controlled release of [D-Trp6]luteinizing hormone-releasing hormone from injectable microcapsules. Proc. Natl. Acad. Sci. USA 81: 5845–5848.

  18. 18

    Sanders, L.M., Kent, J.S., McRae, G.I., Vickery, B.H., Tice, T.R., Lewis, D.H. 1984. Controlled release of a leutinizing hormone-releasing hormone analogue from poly(DL-lactide-co-glycolide) microspheres. J. Pharm. Sci. 73: 1294–1297.

  19. 19

    Hutchinson, F.G., Furr, B.J.A. 1985. Biodegradable polymers for the sustained release of peptides. Biochem. Soc. Trans. 13: 520–523.

  20. 20

    Singh, M., Taforo, T., Laderman, K., Rana, S. 1988. Release of a model protein from biodegradable poly(DL-lactide-co-glycolide) microcapsules. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 15: 456–457.

  21. 21

    Katre, N., Knauf, M. 1988. Succinylated interleukin-2 for pharmaceutical compositions. PCT International Publication number WO 88/01511.

  22. 22

    Katre, N.V., Knauf, M.J., Laird, W.J. 1987. Chemical modification of recombinant interleukin-2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model. Proc. Natl. Acad. Sci. USA 84: 1487–1491.

  23. 23

    Pitt, C.G., Gratzl, M.M., Jeffcoat, A.R., Zweidinger, R., Schindler, A. 1979. Sustained drug delivery systems II: factors affecting release rate from poly(-caprolactone) and related biodegradable polyesters. J. Pharm. Sci. 68: 1534–.

  24. 24

    Visscher, G.E., Pearson, J.E., Fong, J.W., Argentieri, G.J., Robison, R.L., Maulding, H.V. 1988. Effect of particle size on the in vitro and in vivo degradation rates of poly(DL-lactide-co-glycolide) microcapsules. J. Biomed. Mater. Res. 22: 733–746.

  25. 25

    Rosenberg, S.A., Grimm, E.A., McGrogan, M., Doyle, M., Kawasaki, E., Koths, K., Mark, D.F. 1984. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science 223: 1412–1415.

  26. 26

    Gillis, S., Ferm, M.M., Ou, W., Smith, K.A. 1978. T-cell growth factor: parameters of production and a quantitative microassay for activity. J. Immunol. 120: 2027–2032.

  27. 27

    Watson, J., 1979. Continuous proliferation of murine antigen-specific helper T-lymphocytes in culture. J. Exp. Med. 150: 1510–1519.

  28. 28

    Gearing, A.J.H., Thorpe, R. 1988. The international standard for human interleukin-2. Calibration by international collaborative study. J. Immunol. Methods 114: 3–9.

Download references

Author information

Affiliations

  1. Cetus Corporation, 1400 Fifty-Third Street, Emeryville, CA, 94608

    • Maninder Singh Hora
    • , Rajsharan K. Rana
    • , Jack H. Nunberg
    •  & Thomas R. Tice
  2. Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL, 35205

    • Richard M. Gilley
    •  & Michael E. Hudson

Authors

  1. Search for Maninder Singh Hora in:

  2. Search for Rajsharan K. Rana in:

  3. Search for Jack H. Nunberg in:

  4. Search for Thomas R. Tice in:

  5. Search for Richard M. Gilley in:

  6. Search for Michael E. Hudson in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/nbt0890-755

Further reading