TCR-Mimic Antibodies to Intracellular Protein Target
Human antibodies are designed to react with peptide fragments of oncogenic proteins on the cell surface to kill cancer cells. (1)
Targeted Alpha Particle Therapy
Alpha particles are short-ranged high-energy radiations capable of killing in a range of 1 to 3 cells. We are attempting to deliver alpha-emitting isotopes to leukemia cells and small solid tumors using antibodies as ligands. Bi-213 and Ac-225 are purified and chelated to the Ig. Biochemistry of the agents, radiobiology, and pharmacology are studied. Model systems under study include myeloid leukemias, prostate cancer, and lymphoma. Human trials are initiated once clinical scale-up is accomplished. (2)
Oncogene Fusion Gene Product Vaccines
Many leukemias and some solid cancers are associated with chromosome translocations that result in fusion genes and fusion protein products. The amino acid sequences of these fusion proteins, or mutated sequences, can be used to develop tumor-specific vaccines for treating humans. The first such vaccine for treating chronic myelogenous leukemia (using the bcr/abl fusion point) was developed by our laboratory and is currently being used to treat patients. We are also examining the use of mutated heteroclitic peptides with higher avidity for the HLA molecule to use as immunogens.
We are developing methods and strategies to construct complex molecules with multifunctional capabilities for diagnosis and/or therapy that might be self-assembling in vivo by use of synthetic nanomaterials and biological ligands.
Actinium Chelate Chemistry
Actinium-225 is a daughter of thorium-229, which derives from U-233. Actinium can be used to produce Bi-213 in a reusable generator or used alone as an agent for radio-immunotherapy. We are developing methods to attach Ac-225 to proteins for therapeutic use.