Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-27T02:09:58.094Z Has data issue: false hasContentIssue false

Evaluation of Cytokine Delivery Systems for Cancer Immunotherapy

Published online by Cambridge University Press:  15 February 2011

Y.S. Jong
Affiliation:
Artificial Organs Laboratory, Brown University, Providence RI 02912
N.K. Egilmez
Affiliation:
Molecular Immunology, Roswell Park Cancer Institute, Buffalo NY 14263
J.S. Jacob
Affiliation:
Artificial Organs Laboratory, Brown University, Providence RI 02912
L.P. Smith
Affiliation:
Artificial Organs Laboratory, Brown University, Providence RI 02912
T.S. Mottl
Affiliation:
Artificial Organs Laboratory, Brown University, Providence RI 02912
R.B. Bankert
Affiliation:
Molecular Immunology, Roswell Park Cancer Institute, Buffalo NY 14263
E. Mathiowitz
Affiliation:
Artificial Organs Laboratory, Brown University, Providence RI 02912
Get access

Abstract

Cytokines are ideal candidates for controlled release systems; they typically have short half-lives in vivo and may be more effective with localized delivery. A novel microencapsulation technique, phase inversion nanoencapsulation (PIN), was used to encapsulate interleukin-2 or interleukin-12 in biodegradable polymer microspheres. Cytokine was quantified by ELISA and bioactivity analyzed using a murine cytotoxic Tcell line proliferation assay. The release rates of IL-2 was dependant on release buffer components; inclusion of 10% fetal calf serum resulted in significantly higher release rates compared to plain buffer. Encapsulated IL-2 remained stable at all timepoints assayed (up to 4 months) when stored at 4 °C. Results indicated that PIN can be used to encapsulate IL-2 and IL-12, which were released throughout the duration of the release study (up to one month). These microsphere formulations have shown tumor suppressive affects in vivo and may provide a viable alternative to gene transfer for cancer immunotherapy.

Type
Research Article
Copyright
Copyright © Materials Research Society 1999

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Donohue, J.H., Rosenstein, M., Chang, A.E., Lotze, M.T., Robb, R.J., Rosenberg, S.A., J. Immunology. 132(4) pp 1232128 (1984).Google Scholar
2. Nishimura, T., Togashi, Y., Goto, M., Yagi, H., Uchiyama, Y., Hashimoto, Y.. Cancer Immunol Immunother. 21 pp 1218 (1986).Google Scholar
3. Morikawa, K., Okada, F., Hosokawa, M., Kobayashi, H.. Cancer Res. 47 pp 3741 (1987).Google Scholar
4. Bubenik, J., Voitenok, N.N., Kieler, J., Prasslov, V.S., Chumakov, P.M., Bubenikova, D., Simova, J., Jandlova, T.. Immunol Lett. 19 pp 7982 (1988).Google Scholar
5. Hora, M.S., Rana, R.K., Nunberg, J.H., Tice, T.R., Gilley, R.M., Hudson, M.E.. Biotechnology. 8 pp 755758 (1990).Google Scholar
6. Golumbek, P.T., Azhari, R., Jaffee, E.M., Levitsky, H.I., Lazenby, A., Leong, K., Pardoll, D.M.. Cancer Res. 53 pp 58415844 (1993).Google Scholar
7. Liu, L-S., Liu, S-Q., Ng, S.Y., Froix, M., Ohno, T., Heller, J.. J. Control. Rel. 30 pp 241251 (1997).Google Scholar
8. Chen, L., Apre, R.N., Cohen, S.. J. Control. Rel. 43 pp 261272 (1997).Google Scholar
9. Mathiowitz, E., Jacob, J.S., Jong, Y.S., Carino, G.P., Chickering, D.C., Santos, C.A., Vijayaraghavan, K., Montgomery, S., Bassett, M., Morrell, C.. Nature. 386 pp 410414 (1997).Google Scholar
10. Egilmez, N.K., Jong, Y.S., Jacobs, J.S., Santos, C.A., Mathiowitz, E., Iwanuma, Y., Bankert, R.B.. Cancer Immunol Immunother. 46 pp 2124 (1998).Google Scholar