Immunomedics' chemistry group focuses on the identification and preclinical development of tumor-associated therapeutic and diagnostic targeting agents. These agents include tumor-associated monoclonal antibodies (MAbs), receptor-targeting peptides and, more recently, combined antibody and peptide pretargeting combinations. Read More
'Pretargeting', as currently being developed by Immunomedics and IBC Pharmaceuticals, Inc. (a subsidiary of Immunomedics) scientists, may allow a new generation MAb-based diagnostic and therapeutic agents to be developed. This approach uses a 'two-step' protocol. A humanized bispecific antibody (bsAb), with at least one arm that recognizes a tumor-associated antigen and at least one other arm that recognizes an epitope on a diagnostic or therapy agent, is given as a first injection. When non-tumor-targeted bsAb has substantially cleared non-target tissues and has reached a maximum level in the tumor, the bsAb-recognizable diagnostic or therapy agent is given. The latter agents either target to the bsAb localized at the tumor, or they are rapidly cleared through urine via the kidneys. In preclinical animal work, to date, high tumor to normal tissue localization ratios have been seen (Cancer Research 59:4400-4405, 1999), indicating excellent contrast for diagnostic purposes, and substantially improved ratios for therapy applications.
Importantly, our pretargeting methodology relies on the second arm of the tumor-targeting bispecific binding to a molecule that can be attached to any diagnostic or therapeutic agent. Because of this, the technology potentially comprises a universally useful system, not requiring the generation of a new second antibody for each and every individual diagnostic or therapeutic agent. Currently in preclinical studies are applications directed toward improved diagnostic agents based on technetium-99m for SPECT, and for the very sensitive detection modality, positron emission tomography. On the therapy side, we have expanded the range of useful 'two-step' therapy agents from radionuclides to anti-cancer chemotherapy drugs, ribonucleases, and enzyme prodrug therapy (ADEPT). Each of these applications is being studied either in our laboratories or in the collaborating laboratories of leading research institutions. Read More
Together with IBC Pharmaceuticals, Inc., We have developed a new platform technology, called the DOCK-AND-LOCKTM method, or DNLTM, which has the potential for making a considerable number of bioactive molecules of increasing complexity. DNLTM utilizes the natural interaction between two proteins, cyclic AMP-dependent protein kinase, or PKA, and A-kinase anchoring proteins, or AKAPs. The region that is involved in such interaction for PKA is called the dimerization and docking domain, or DDD, which always appears in pairs. Its binding partner in AKAPs is the anchoring domain, or AD. When mixed together, DDD and AD will bind with each other spontaneously to form a binary complex, a process termed docking. Once “docked,” certain amino acid residues incorporated into DDD and AD will react with each other to “lock” them into a stably-tethered structure. Since DDD always appears in pairs, any component that is linked to DDD will have two copies present in the final products. The outcome of DNLTM is the exclusive generation of a stable complex, in a quantitative manner that retains the full biological activities of its individual components. A description of the DNLTM platform technology was published in the September 15, 2007, Supplement issue of Clinical Cancer Research. Read More
Many of our core radiolabeling technologies evolved from our original work on MAbs to receptor-targeting peptides. In turn, some of the radiolabeling methods developed for the peptide applications, together with our extensive prior radiolabeling experience, has led to novel radioimmunotherapy (RAIT) agents for application within 'pretargeting' formats. Read More