The rearrangements of immunoglobulin and T-cell antigen receptor gene were analyzed to develop approaches for the classification of neoplasms of uncertain lineage, to define the state of differentiation of neoplastic B-cell and T-cell precursors, and to determine the mechanisms that lead to the failure of maturation of such precursor cells. These studies have culminated in the development of new approaches for the diagnosis and monitoring the therapy of T- and B-cell lymphoid neoplasia. Furthermore, studies were directed toward defining the role played by the inducible receptor for interleukin-2 (IL-2) in the proliferation of normal and malignant T lymphocytes. Using a monoclonal antibody (anti-Tac) to the Il-2 receptor, this receptor was purified, biochemically characterized, and the cDNAs hybridizing with it were molecularly cloned, sequenced, and expressed. In contrast to normal resting T cells, human T cell lymphotrophic virus-I (HTLV-I)-associated adult T-cell leukemia (ATL) cells constitutively express large numbers of IL-2 receptors which may be aberrant. The anti-Tac monoclonal antibody was used in the therapy of the now universally fatal, Tac-expressing ATL. One of three patients treated underwent a complete remission lasting 6 months. In additional studies, ricin A, Pseudomonas exotoxin, and the alpha-emitting isotope of bismuth were conjugated to the anti-Tac monoclonal antibody. These antibody conjugates effectively killed Tac-expressing tumor lines at concentrations that did not affect the viability of Tac-nonexpressing T lymphocytes.
