Cancer Immunity 12:11 (2012)

The communicative enthusiasm of Lloyd Old Before starting this introduction on the development of monoclonal antibodies for cancer therapy and the role of Lloyd Old in the field, in parallel with his central interest in T cell activation by tumor antigen vaccination, let me say a few subjective words about a unique human quality of Lloyd: his extraordinary communicative enthusiasm. That quality is sometimes called charisma, but there is more to it than that; it is a capacity to communicate your interest to your fellow scientists (in the sense of “love your neighbor” in the scriptures) and to give to your interlocutor the impression of being fully understood. The result was that, when you came out of Lloyd’s office after a scientific dialogue, you felt “boosted” to develop your project with renewed energy and more imagination. Lloyd had this kind of positive influence on so many fields and so many personalities that it is not possible to mention them all. I will first mention, very briefly, the two most representative well-known examples by which Lloyd stimulated and contributed to the field of cancer immunotherapy, and then follow with several other examples in the field of monoclonal antibodies by mentioning the central personalities who worked with him or independently, including myself and a few coworkers from my group who enjoyed the privilege of having interacted with him. While writing this kind of personal review, I kept in mind this question: would Lloyd enjoy reading it and would he agree with the points I am trying to underscore? The first example in the field of immunotherapy was the discovery of the MAGE genes as the source of antigens recognized by tumor-reactive T cells, which was initiated and developed by Thierry Boon’s group in the Brussels Branch of the Ludwig Institute for Cancer Research (LICR) (1, 2). Lloyd himself had pursued passionately the identification of T celldefined tumor antigens. Together with one of his fellows, Alexander Knuth, they systematically analyzed the tumorreactive CD8 T cells, which could be expanded in autologous mixed lymphocyte-tumor cell culture (3). It was subsequently a collaboration of Knuth with Boon that allowed the discovery of MAGE-A1 (1). Furthermore, Lloyd, along with Yao-Tseng Chen, had a central role in the field by the discovery of NY-ESO1 antigen (4) and its broad extension by the definition of the concept of Cancer/Testis (CT) antigens (5). The second major example is the SEREX method, using a bacterial expression library for detecting patients’ serum antibodies reacting with tumor antigens (6). This methodology was described independently by Lloyd’s former collaborator, Michael Pfreundschuh, but Lloyd had already for many years a major interest in the use of patient serum for autologous typing and immensely broadened the application of the SEREX method, up to the description of the immunome (7) and the SEREX database, in collaboration with the late Matthew Scanlan. The antibodies discovered by this technology were not used for therapy, but they represented precious evidence of patients’ immune responses against their own tumors, and, most importantly, SEREX-detected antibodies led to the identification of several new Cancer/Testis antigens, including the most important, NY-ESO-1. In addition to these two emblematic examples, we can say, without risk of contradiction, that since he took over the direction of the LICR in 1988, Lloyd spread his enthusiastic and liberal spirit within all the different branches of LICR.