Diphtheria toxin conjugate therapy of cancer.
The approval by the FDA of ONTAK (DAB389IL2) for CTCL and the encouraging results described above with a number of DT conjugates for different neoplasms suggest that a niche is developing for these biologic agents. Moreover, practicing physicians are becoming more familiar with the side effect profile for these agents, increasing their comfort with using these unique drugs. Finally, the marked synergy observed between standard cytotoxic drugs and other biologics such as Herceptin and Rituximab suggests that similar supra-additive effects may be observed by combining DT conjugates with chemotherapy. In support of this hypothesis, in vitro synergy has been observed between DT388GMCSF and both cytarabine and doxorubicin [84,85]. The future appears to show expanded testing of DT conjugates with likely rapid clinical development, particularly for chemotherapy-resistant hematologic neoplasms and brain tumors.
Frankel
Arthur E
AE
Wake Forest University School of Medicine, Medical Center Drive, Winston-Salem, NC 27157, USA. afrankel@wfubmc.edu
Powell
Bayard L
BL
Lilly
Michael B
MB
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins