TARGETING P53 AS A GENERAL TUMOR-ANTIGEN

A major barrier to the design of immunotherapeutics and vaccines for c ancer is the idiosyncratic nature of many tumor antigens and the possi bility that T cells may be tolerant of broadly distributed antigens. W e have devised an experimental strategy that exploits species differen ces in protein sequences to circumvent tolerance of high-affinity T ce lls. HLA transgenic mice were used to obtain cytotoxic T lymphocytes s pecific for peptides from the human p53 tumor-suppressor molecule pres ented in association with HLA-A2.1. Although such p53-specific cytotox ic T cells did not recognize nontransformed human cells, they were abl e to lyse a wide variety of human tumor cell lines, thus confirming th e existence of broadly distributed determinants that may serve as targ ets for immunotherapy.