Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression.

Objectives: While most women with ovarian cancer will achieve complete remission after treatment, the majority will relapse within two years, highlighting the need for novel therapies. Cancer stem cells (CSC) have been identified in ovarian cancer and most other carcinomas as a small population of cells that can self-renew. CSC are more chemoresistant and radio-resistant than the bulk tumor cells; it is likely that CSC are responsible for relapse, the major problem in cancer treatment.

Genetic alteration of a bispecific ligand-directed toxin targeting human CD19 and CD22 receptors resulting in improved efficacy against systemic B cell malignancy.

A bispecific ligand-directed toxin (BLT) called DT2219ARL consisting of two scFv ligands recognizing CD19 and CD22 and catalytic DT390 was genetically enhanced for superior in vivo anti-leukemia activity. Genetic alterations included reverse orienting VH-VL domains and adding aggregation reducing/stabilizing linkers. In vivo, these improvements resulted in previously unseen long-term tumor-free survivors measured in a bioluminescent xenograft imaging model in which the progression of human Raji Burkitt's lymphoma could be tracked in real time and in a Daudi model as well.

Radiotherapy of CD45-expressing Daudi tumors in nude mice with yttrium-90-labeled, PEGylated anti-CD45 antibody.

Studies were performed to determine the suitability of using the polyethylene glycol (PEG)-labeled AHN-12 anti-CD45 monoclonal antibody to deliver the high-energy beta-particle-emitting isotope 90Y to a CD45+ B-cell Daudi lymphoma grown as flank tumors in athymic nude mice. The PEGylated radiolabeled antibody displayed a significantly better antitumor effect in the mouse tumor flank model (p<0.03) and significantly better blood pharmacokinetics in normal rats (p<0.