An array of immunotherapeutic strategies for B-cell lymphomas

With FDA approval of monoclonal antibodies (mAb) against the B-cell-specific cell surface molecule CD20, immunotherapy in B-cell non-Hodgkin's-lymphomas (NHL) has gained momentum. Since the first description of the CD20 mAb and its use in a single patient, it has taken more than 20 years to implement this in current treatment options. NHLs are of particularly interest to the research community, since a whole array of novel immunotherapeutic strategies are currently in development. Unconjugated and radioconjugated mAbs are either approved, or in Phase III trials with very promising results. Adoptive transfer of polyclonally activated, tumour-specific or antigen-specific T-cells are in Phase I and II trials. Even antisense approaches have reappeared in the treatment of NHL. However, it is not only passive immunotherapy that has evolved. There are several new strategies for vaccination in NHL, whilst older approaches are under revision. Vaccine strategies targeting the tumour cell specific clonal idiotype (Id) have been refined and, with the identification of T-cell responses against shared epitopes, vaccination against the clonal Id might finally become clinically applicable. Significant progress has also been made in the development of cellular vaccines. Malignant B-cells are turned into 'tumour-APC' and are used to stimulate T-cell responses in Phase I trials. Moreover, with the identification of universal tumour antigens, another antigen-specific vaccine for NHL can be envisioned. By combining this array of very promising tools, immunotherapy might finally become a standard modality for the treatment of B-cell malignancies.