We have developed an immunotoxin SS1P that targets ovarian cancers, mesotheliomas and pancreatic cancers that is currently in clinical trials. In collaboration with our CRADA partner ENZON we are carrying out laboratory experiments to produce improved forms of SS1P. One approach is to modify SS1P with high molecular weight polyethylene glycol to decrease immunogenicity and increase half-life in the circulation. Many mutants of SS1P have been produced to allow site-specific modification with PEG. Hematopoietic Tumors- Immunotoxin BL22 has shown excellent clinical activity in patients with Hairy Cell Leukemia. To increase the usefulness of BL22 in other leukemias and lymphomas we have mutated the protein to increase its affinity for CD22 and also mutated the toxin to increase its ability to reach the cytosol and kill target cells. An improved form of BL22 called HA22 is being prepared for a clinical trial in chronic lymphocytic leukemia. Other high affinity forms of BL22 are now being prepared. CD30 is expressed on cells from Hodgkin's disease and anaplastic large cell lymphoma. A series of new antibodies to CD30 have been produced. Two of these MAbs bind to an epitope not present on solulbe CD30 and should be especially useful for targeted therapy. 8H9 is a monoclonal antibody developed by Dr. Cheung at Sloan Kettering that targets an antigen expressed on many childhood cancers and breast cancer. We have produced a recombinant immunotoxin that kills cells expressing the 8H9 antigen and are currently doing safety studies in monkeys prior to a clinical trial.

National Institute of Health (NIH)
Division of Basic Sciences - NCI (NCI)
Intramural Research (Z01)
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Basic Sciences
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Kaplan, Gilad; Mazor, Ronit; Lee, Fred et al. (2018) Improving the In Vivo Efficacy of an Anti-Tac (CD25) Immunotoxin by Pseudomonas Exotoxin A Domain II Engineering. Mol Cancer Ther 17:1486-1493
Shancer, Zoe; Williams, Matthew; Igelman, Austin et al. (2018) Preclinical development of anti-BCMA immunotoxins targeting multiple myeloma. Antib Ther 1:19-25
Mazor, Ronit; Addissie, Selamawit; Jang, Youjin et al. (2017) Role of HLA-DP in the Presentation of Epitopes from the Truncated Bacterial PE38 Immunotoxin. AAPS J 19:117-129
Mazor, Ronit; Kaplan, Gilad; Park, Dong et al. (2017) Rational design of low immunogenic anti CD25 recombinant immunotoxin for T cell malignancies by elimination of T cell epitopes in PE38. Cell Immunol 313:59-66
Bera, Tapan K; Onda, Masanori; Kreitman, Robert J et al. (2014) An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies. Leuk Res 38:1224-9
Sathyanarayana, Bangalore K; Hahn, Yoonsoo; Patankar, Manish S et al. (2009) Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeats. BMC Struct Biol 9:1
Ochiai, Hidenobu; Archer, Gary E; Herndon 2nd, James E et al. (2008) EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells. Cancer Immunol Immunother 57:115-21
Du, Xing; Beers, Richard; Fitzgerald, David J et al. (2008) Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activity. Cancer Res 68:6300-5
Du, Xing; Nagata, Satoshi; Ise, Tomoko et al. (2008) FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxins. Blood 111:338-43
Epel, Malka; Carmi, Irit; Soueid-Baumgarten, Sharon et al. (2008) Targeting TARP, a novel breast and prostate tumor-associated antigen, with T cell receptor-like human recombinant antibodies. Eur J Immunol 38:1706-20

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