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Human monoclonal antibody-based immunotherapy
Our laboratory focuses on the engineering and use of human antibodies in discovery research and disease treatment. We are working in three disease areas: cancer, emerging infectious diseases, and HIV/AIDS – a breadth of investigation made possible by the development and use of state-of-the-art tools in the field of antibody engineering that support our research efforts. More recently, we have been developing humanized mice to support our targeted immunotherapy studies and to investigate the roles of human adult stem cells in regenerative medicine.
We have active research programs in cancer immunotherapy that include the following targets: CXCR4 for breast cancer, G250 (CA IX) for renal cell carcinoma, CCR4 for cutaneous T cell lymphomas (CTCLs), and IGHV1-69 encoded B-cell receptors (BCR) for treatment of an aggressive form of chronic lymphocytic leukemia (CLL). We are also developing immunotherapies that can modulate immune T cell activity to boost natural cancer immunity and response to cancer vaccines. Regulatory T cells (Tregs) exert control by dampening the immune response to prevent host tissue damage, but these cells are also co-opted by cancer cells, which leads to immune evasion. Tregs express high levels of CCR4 and we have demonstrated in vitro and in vivo that anti-CCR4 Mabs can reverse this immune suppression and reverse T cell "exhaustion," thereby restoring host immunity.
We use human monoclonal antibodies in functional and structural studies to understand mechanisms of viral entry; identify common targets that provide broad-spectrum protection; and develop strategies that prevent the viruses from undergoing neutralization escape. Vaccinated/infected humans and humanized mice are the B-cell sources of antibody genes for these studies. We are studying human pathogenic viruses that include influenza A, West Nile Virus, SARS- and MERS-CoVs and HIV/AIDS. As with our cancer studies, we are investigating whether human antibodies that are directed to surface proteins on T-cells or their secreted products can reverse T-cell "exhaustion" which is known to occur in HIV-1/AIDS with the goal of lowering viral loads, prolonging health, and preventing the spread of HIV-1. We are using our humanized mice in the area of anti-microbial immunity to develop broad-spectrum anti-viral vaccines.
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Boston, MA 02215