Our research efforts are currently focused in four areas: The first addressees the development of immunotoxins (ITs) and monoclonal antibodies (MAbs) for the therapy of cancer. We have generated chimeric molecules containing MAbs and chemically modified ricin A chain. These ITs have been tested in vitro, in mice with murine or human tumors, and in humans. Secondly, we are interested in tumor dormancy in both mice and humans. This involves working out the complex interplay between the immune system of the host and the efforts by the tumor to evade the immune system. Thirdly, we have developed a recombinant vaccine against the toxin ricin (a CDC level 2 biothreat). This vaccine is safe and highly protective in mice exposed to ricin aerosol, gavage, or injection. We have completed two clinical trials in human volunteers to demonstrate safety and seroconversion and are currently optimizing doses and dose regimens in mice to further enhance the protection of mucosal surfaces. Finally, we have developed a novel platform to generate synthetic “peptoid” vaccines against HIV, hepatitis C virus and West Nile virus. This involves chemical synthesis of peptoid libraries, screening with monoclonal antibodies known to neutralize the pathogen in question, sequencing and synthesis of selected peptoids and immunization of mice with the peptoids attached to carrier proteins.
Smallshaw, J.E., Ghetie, V., Baluna, R., Fulmer, J.R., Trahan, L.L., Ghetie, M-A., Rizo, J. and Vitetta, E.S. Genetic Engineering of an Immunotoxin to Eliminate Its Ability to Induce Pulmonary Vascular Leak in Mice. Nature Biotechnology, 21:387-397,2003.
Vitetta, E.S., Smallshaw, J.E., Coleman, E., Jafri, H., Foster, C., Munford, R., and Schindler, J. A pilot clinical trial of a recombinant ricin vaccine in normal humans. PNAS 103(7):2268-2273, 2006.
Smallshaw, J.E., Richardson, J.A., and Vitetta, E.S. RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol, Vaccine, 25:7459-7469, 2007.
Brooks, K., Coleman, E., and Vitetta, E. The antitumor activity of an anti-CD54 antibody in SCID mice xenografted with human breast, prostate, non-small cell lung, and pancreatic tumor cell lines. Int J of Cancer, 123:2438-2445, 2008.
Chakravarty, P., Marches, P., Zimmerman, N.S., Swafford, A.D.E., Bajaj, P., Musselman, I.H., Pantano, P., Draper, R., and Vitetta, E.S. Thermal Ablation of tumor cells with antibody-functionalized single-walled carbon nanotubes. PNAS, 105: 8697-8702, 2008.