The specific binding of an antibody to a target molecule (antigen) on the surface of a cell means that monoclonal antibodies (mAbs) can be used to elicit an immune response against the target cell, block a receptor protein involved in cancer onset or progression, or deliver a toxin or radioisotope payload to destroy the cell. Radioisotopes bound to mAbs can also be used to visualize tumors and obtain diagnostic and prognostic data.
There are several antibody-based therapies are currently available to cancer patients, but these often cause dose-limiting side effects as they target both healthy and cancer cells. To reduce the toxicity caused by mAbs binding to normal cells, LICR is exploring the potential of mAbs that target cell surface molecules expressed selectively on cancer cells. These mAbs are being engineered to deliver chemotherapeutics, radioisotopes (radioimmunotherapy; RIT), nanoparticles, and small interfering RNA (siRNA) molecules directly to cancer cells. The mAbs are also being engineered so that they can be used to detect and visualize tumors for both diagnostic and prognostic purposes.
Some targeted antibody candidates generated and/or characterized by LICR are:
- cG250 (Rencarex® / Redectane®)—targets the CA-IX molecule on renal cell carcinoma (RCC, kidney cancer). The antibody is in phase III clinical trials as a diagnostic tool and as a therapeutic modality.
- MORAb-003 (farletuzumab)—targets the folate receptor alpha, which is over-expressed on a number of epithelial cancers, including ovarian, breast, renal, lung, colorectal and brain cancers. The antibody was licensed to Morphotek Inc., and is in a phase III trial for ovarian cancer therapy.
- hu806—targets the over-expressed form of the epidermal growth factor receptor (EGFR) present in 50% of all cancers of epithelial origin. The antibody was licensed to spin-off company Life Sciences Pharmaceuticals and is now being taken into clinical development by the pharmaceutical company Abbott.
- hu3S193—targets the Ley antigen present on several types of cancer. The antibody is in phase II clinical trials being conducted by LICR spin-off company Recepta Biopharma
- huA33—targets the A33 antigen present on colorectal cancer cells. The antibody has been licensed to LICR spin-off company Life Sciences Pharmaceuticals, and the mAb’s therapeutic potential is being tested as a stand-alone antibody, as a radioimmunotherapy agent, and in combination with chemotherapy.