DF/HCC Program Affiliation

Lymphoma and Myeloma
Translational Pharmacology and Early Therapeutic Trials

Research Abstract

Monoclonal antibody (mAb) therapies are currently unavailable for human multiple myeloma (MM). I recently characterized cell surface glycoprotein CS1 (CD2 subset 1, CRACC, SLAMF7, CD319 or 19A24) to be a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 is universally and highly expressed on patient MM cells but not other normal tissues. HuLuc63 specifically induces ADCC against CS1-expressing MM cells and potently regress tumors in a human plasmacytoma xenograft model. We are currently defining biological function and the role of CS1 in MM pathophysiology using laboratory and animal models in order to set the stage for targeting CS1 in new MM therapies. On the other hand, we are studying BAFF/APRIL pathways in MM and test whether targeting this pathway by anti-B cell maturation antigen (BCMA) mAb induces cytotoxicity against MM cells. These studies will help to combine mAb-based immunotherapies and small molecular inhibitors both targeting essential/key growth and survival pathways in order to maximize killing of MM cells without overt cytotoxicity. Thus, such translational researches will eventually improve patient outcome in MM.

Publications

• van Haaften G,Dalgliesh GL,Davies H,Chen L,Bignell G,Greenman C,Edkins S,Hardy C,O'Meara S,Teague J,Butler A,Hinton J,Latimer C,Andrews J,Barthorpe S,Beare D,Buck G,Campbell PJ,Cole J,Forbes S,Jia M,Jones D,Kok CY,Leroy C,Lin ML,McBride DJ,Maddison M,Maqu
  19330029
• Tai YT,Soydan E,Song W,Fulciniti M,Kim K,Hong F,Li XF,Burger P,Rumizen MJ,Nahar S,Podar K,Hideshima T,Munshi NC,Tonon G,Carrasco RD,Afar DE,Anderson KC.CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated i
  19196658
• Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L, Podar K, Hideshima T, Chauhan D, Raje N, Schlossman R, Richardson P, Munshi NC, Anderson KC.Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow
  16818641
• Tai YT, Li XF, Catley L, Coffey R, Breitkreutz I, Bae J, Song W, Podar K, Hideshima T, Chauhan D, Schlossman R, Richardson P, Treon SP, Grewal IS, Munshi NC, Anderson KC.Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced
  16357183
• Tai YT, Li X, Tong X, Santos D, Otsuki T, Catley L, Tournilhac O, Podar K, Hideshima T, Schlossman R, Richardson P, Munshi NC, Luqman M, Anderson KC.Human anti-CD40 antagonist antibody triggers significant antitumor activity against human multiple myeloma
  15994968
• Tai YT, Catley LP, Mitsiades CS, Burger R, Podar K, Shringpaure R, Hideshima T, Chauhan D, Hamasaki M, Ishitsuka K, Richardson P, Treon SP, Munshi NC, Anderson KC.Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human mu
  15087402