Wayne Marasco

Dana Farber Cancer Institute
44 Binney Street - JFB 824
Boston, MA 02115
Tel: (617) 632-2153
Fax: (617) 632-3113
Email: wayne_marasco@dfci.harvard.edu

Our laboratory research focuses on the engineering of human antibodies and the use of human antibodies in discovery research and disease treatment. We are working in three disease areas: cancer, emerging infectious diseases, and HIV/AIDS. We have constructed and characterized of one of the largest human antibody phage display libraries ever made, and now comprising 27 billion members. Numerous human antibody engineering discoveries in our laboratory have allowed us to validate the quantity and high quality of the human antibodies in this library. Our laboratory uses all of the modern molecular techniques to isolate and characterize human monoclonal antibodies including phage, yeast and mammalian display, human CD34+ stem cell reconstructed mice, memory B-cell immortalization by EBV and TLR4 ligands, in silico modeling and co-crystallographic studies. We have all of the expertise necessary to move human Mabs into clinical trials.

Our laboratory is pursuing active research programs in human monoclonal antibody immunotherapy that include the following cancer targets: CXCR4 in breast cancer, G250 (CA IX) in renal cell carcinoma, CCR4 in cutaneous T cell lymphomas (CTCLs), and GITR and PD1-L in the modulation of T regulatory cell function to boost natural cancer immunity and responses to cancer vaccines. We also founded the National Foundation for Cancer Research Center for Therapeutic Engineering (NFCR-CTAE) to assist cancer investigators with the isolation and characterization of new anti-cancer human monoclonal antibodies (see www.NFCR-CTAE.org).

In the field of infectious diseases, we are studying targets that include SARS-CoV spike protein in severe acute respiratory syndrome, the E-protein in West Nile virus, hemagglutin and neuraminidase in Avian influenza H5N1, and the chemokine/HIV coreceptors CCR5 and CXCR4 in HIV/AIDS. Our research program in human T cell lymphotropic virus type I (HTLV-I,) associated with adult T cell leukemia (ATL), focuses on understanding the mechanisms of leukemogenesis and the development of new treatments for this fatal type of leukemia.

References:

• Sui J, Li W, Roberts A, Matthews LJ, Murakami A, Vogel L, Wong SK, Subbarao K, Farzan M, and Marasco WA. Evaluation of Human mAb 80R in Immunoprophylaxis of SARS by an Animal Study, Epitope Mapping and Analysis of Spike Variants. J.Virol. 2005 May;79(10):5900-6.
• Gould LH, Sui J, Foellmer H, Wang T, Ledizet M, Murakami A, Noonan K, Lambeth C, Kar K, Anderson JF, de Silva A, Koski R, Marasco WA, and Fikrig E. Protection and therapeutic capacity of human single-chain-Fc fusion proteins against West Nile virus. J. Virol. 2005 Dec;79(23):14606-14613.
• Xu C, Sui J, Tao H, Aird D, Zhu QK and Marasco WA. Human Anti-CXCR4 Antibodies Undergo VH Replacement, Exhibit Functional V-Region Sulfation and Define CXCR4 Antigenic Heterogeneity. J. Immunol 2007 Aug 15;179(4):2408-18.
• Marasco WA and Sui J. The growth and potential of human antiviral monoclonal antibody therapeutics. Xu C, Sui J, Tao H, Aird D, Zhu QK and Marasco WA. Nat Biotechnol. 2007 Dec;25(12):1421-34.