We are a translational immunology lab that takes novel discoveries into clinical trials in humans. Our research efforts are focused in four areas: The first addresses the development of immunotoxins (ITs) and monoclonal antibodies (MAbs) for the therapy of lymphoma, graft versus host diseases (GVHD), breast cancer and AIDS. We have generated chimeric molecules containing MAbs and chemically modified or recombinant ricin A chain. These ITs have been tested in vitro, in mice with murine or human tumors, and more recently in humans with advanced lymphoma, myeloma, melanoma and GVHD. We are studying their mode of action, ways to improve their potency, and strategies to decrease their non-specific toxicity and immunogenicity in vivo. Secondly, we are developing genetically engineered, chimerized MAbs with improved therapeutic activity, MAbs that signal cell cycle arrest and apoptosis, reverse multidrug resistance in tumor cells, or which target carbon nanotubes to tumor cells. These are all being tested in vitro and in mice with the long-term goal of using them in humans. Thirdly, we are studying immunologic mechanisms involved in tumor dormancy and escape from dormancy. Using a mouse model of B cell lymphoma, we are studying the nature of the host mechanisms and, in particular, focusing on regulatory T cells. Finally we are developing novel vaccine mimetics and recombinant proteins for use in vaccines against toxins and pathogens. One of our vaccines has shown promising results in a clinical trial conducted at UTSW and is moving on to more advanced development.
RESEARCH INTERESTS
Antibody-based therapies
Cancer Dormancy
Vaccines
Nanotechnology
RECENT PUBLICATIONS
Ghetie, M-A., Marches, R., Kufert, S., Vitetta, E.S., "An anti-CD19 antibody inhibits the interaction between P-gp and CD19, causes P-gp to translocate out of lipid rafts and chemosensitizes a multi-drug resistant lymphoma cell line" Blood, 104:1:178-183, 2004
Smallshaw, J., Richardson, J.A., Pincus, S., Schindler, J., and Vitetta, E.S., "Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin" Vaccine, 23:39:4775-4784, 2005
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, Spring 2006
Liu, X., Pop, L., Smallshaw, J.E., Ghetie, V., Vitetta, E.S, "Generation and characterization of a novel tetravalent anti-CD22 antibody with improved antitumor activity and pharmacokinetics" Int Immunopharma, 6:5:791-799, 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
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