There’s no “magic bullet” for cancer. Or is there?

2001

Challenge

In the U.S., it is expected that approximately 1.7 million people will be diagnosed with cancer each year, and one third of those will die of the disease. To combat such a complex and multifactorial disease, doctors need more efficient and targeted treatments to destroy cancers cells without harming healthy tissues.

Advance

IRP researcher Ira Pastan, M.D., and colleagues created a new type of cancer drug, termed recombinant immunotoxins, that specifically target cancer cells. These “magic bullets” are made by genetically engineering a potent bacterial toxin, Pseudomonas exotoxin A, with an antibody fragment that selectively binds to receptors on the cancer cell surface and delivers the toxin to the cancer cells.

Impact

Delivering a toxic payload to the inside of a cancer cell while leaving healthy tissue unscathed is a major step forward in the battle against cancer, as many harmful side effects will be minimized. After years of research and clinical trials, moxetumomab pasudotox, a first-generation immunotoxin, was approved by the FDA in September 2018 for certain adults with hairy cell leukemia, providing a promising new therapy to a group of patients who previously had few other options.

Publications

Onda M, Olafsen T, Tsutsumi Y, Bruland ØS, Pastan I. (2001). Cytotoxicity of Antiosteosarcoma Recombinant Immunotoxins Composed of TP-3 Fv Fragments and a Truncated Pseudomonas Exotoxin A. J Immunother 1991. 24(2), 144-150.

Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, Fitzgerald DJ, Lechleider R, Pastan I. (2012). Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 30(15), 1822-8.

Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, FitzGerald DJ, Santiago L, Gao G, Lanasa MC, Pastan I. (2018). Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood. 131(21):2331-2334.

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, Gladstone DE, le Coutre P, Dietrich S, Gotic M, Larratt L, Offner F, Schiller G, Swords R, Bacon L, Bocchia M, Bouabdallah K, Breems DA, Cortelezzi A, Dinner S, Doubek M, Gjertsen BT, Gobbi M, Hellmann A, Lepretre S, Maloisel F, Ravandi F, Rousselot P, Rummel M, Siddiqi T, Tadmor T, Troussard X, Yi CA, Saglio G, Roboz GJ, Balic K, Standifer N, He P, Marshall S, Wilson W, Pastan I, Yao NS, Giles F. (2018). Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 32(8):1768-1777.