Immunotherapy of Hodgkin's lymphoma

Many new treatment approaches have given promising results in experimental Hodgkin's lymphoma (HL) models. Early clinical trials evaluating antibody based compounds as immunotoxins (ITs), radioimmunotherapy (RIT), bispecific molecules (BSMs), and recently monoclonal antibodies (MAbs), have demonstrated some clinical efficacy in patients with advanced refractory or relapsed HL. In addition, cellular immunotherapy is evolving. Although it seems unlikely to cure chemotherapy resistant patients with larger tumor masses by either of these approaches alone, the combination with conventional chemotherapy might help to overcome resistance of Hodgkin-/ReedSternberg (H-RS) cells. Another rationale for the development of these immunotherapies is to eliminate residual disease and thereby to prevent relapses from the disease. Currently, several clinical studies are running. A murine MAb (Ki-4) based 131 Iodine conjugate has shown efficacy in refractory HL patients in a phase II study, but less toxic constructs using alternate MAbs or isotopes should be developed. A humanized as well as a fully human anti-CD30 MAb are being tested in clinical phase I/II studies. These MAbs could engage the human immune system against the H-RS cells. In addition, these MAbs could be then combined with conventional chemotherapy in order to improve the treatment of HL.