Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy

  • Authors:
    • Erwin R. Boghaert
    • Kiran Khandke
    • Latha Sridharan
    • Douglas Armellino
    • Maureen Dougher
    • John F. DiJoseph
    • Arthur Kunz
    • Philip R. Hamann
    • Ashwin Sridharan
    • Stanley Jones
    • Carolyn Discafani
    • Nitin K. Damle
  • View Affiliations

  • Published online on: March 1, 2006     https://doi.org/10.3892/ijo.28.3.675
  • Pages: 675-684
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Calicheamicin is a potent chemotherapeutic with a low therapeutic index that requires targeting to tumor cells for its use in the clinic. To treat acute myeloid leukemia, calicheamicin has been conjugated to an antibody that recognizes CD33 (gemtuzumab ozogamicin). The application range of this ‘active’ targeting strategy is limited since it depends on specific antigen expression by tumor cells. This limitation could be reduced by using an antigen-independent ‘passive targeting’ strategy for calicheamicin. ‘Passive targeting’ relies on the dysfunctional vasculature of a neoplastic tumor that allows enhanced retention of macromolecules. We studied the efficacy of calicheamicin conjugated to various carrier molecules: i.e. immunoglobulin, albumin or PEGylated Fc fragments. In nude mice, a conjugate of anti-CD33 and calicheamicin accumulates in human tumor xenografts in the absence of detectable amounts of targeting antigen. Passive targeting provided sufficient accumulation of this conjugate to inhibit tumor growth of 10 different CD33-negative xenograft models. This efficacy depended on the use of an acid-labile linker between antibody and calicheamicin. Substitution of immunoglobulin as a carrier with either albumin or PEGylated Fc reduced or eliminated the efficacy of the conjugate. The results showed that using ‘non-specific’ immunoglobulin for passive targeting of calicheamicin might be an effective mode of cancer therapy.

Related Articles

Journal Cover

March 2006
Volume 28 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Boghaert ER, Khandke K, Sridharan L, Armellino D, Dougher M, DiJoseph JF, Kunz A, Hamann PR, Sridharan A, Jones S, Jones S, et al: Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy. Int J Oncol 28: 675-684, 2006
APA
Boghaert, E.R., Khandke, K., Sridharan, L., Armellino, D., Dougher, M., DiJoseph, J.F. ... Damle, N.K. (2006). Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy. International Journal of Oncology, 28, 675-684. https://doi.org/10.3892/ijo.28.3.675
MLA
Boghaert, E. R., Khandke, K., Sridharan, L., Armellino, D., Dougher, M., DiJoseph, J. F., Kunz, A., Hamann, P. R., Sridharan, A., Jones, S., Discafani, C., Damle, N. K."Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy". International Journal of Oncology 28.3 (2006): 675-684.
Chicago
Boghaert, E. R., Khandke, K., Sridharan, L., Armellino, D., Dougher, M., DiJoseph, J. F., Kunz, A., Hamann, P. R., Sridharan, A., Jones, S., Discafani, C., Damle, N. K."Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy". International Journal of Oncology 28, no. 3 (2006): 675-684. https://doi.org/10.3892/ijo.28.3.675