Novel Strategies to Improve Rituximab Efficacy in Non-Hodgkin's Lymphomas

Abstract

005eertechz thrombocytopenia, hypotension, anemia, bronchospasm, urticaria, headache, abdominal pain, and arrhythmia. These adverse reactions were usually reversible with appropriate treatment. Only rare cases of death were reported [7].Despite the great therapeutic value of Rituximab, many treated patients relapse or become resistant after treatment. Rituximab resistance is due to depletion of complement and effector cells, alteration in complement regulatory protein expression, polymorphisms in FcγRIIIa, selection of neoplastic cells expressing mutated or not expressing CD20 antigen [8]. In order to overtake these limitations different strategies have been exploited.The first strategy consists in the augment of Rituximab potency and efficacy by the conjugation to a radionuclide [9] A different strategy to improve the results obtained with Rituximab is based on the selection of new engineered anti-CD20 antibodies characterized by reduced immunogenicity and/or enhanced binding affinity for CD20 antigen and for the FcγRIIIa receptor on effector NK cells. A first group of engineered antibodies (also named second generation anti-CD20 mAbs) has been developed with the intent to reduce immunogenicity; it consists of humanised molecules, with murine portion restricted to only hypervariable regions, or fully human molecules (OFA, veltuzumab, and ocrelizumab). A second group (also named third generation anti-CD20 mAbs) consists of engineered antibodies with humanised CDR and modified Fc regions, to augment binding affinity for the FcRIIIa receptor and consequently ADCC (rhumAb v114, ocaratuzumab, obinutuzumab, TRU-015, EMAB-6) [2,4]. Most of these new mAbs are still in clinical trials and several positive results have been reported, despite their complete clinical potential has not been yet exploited.Certainly, the availability of a panel of human anti-CD20 mAbs EditorialNon-Hodgkin's lymphomas (NHLs) are the second fastest growing cancer in terms of incidence and deaths in the United States and Europe. NHLs are a heterogeneous cancer group including several haematological neoplasias with different degree of aggressiveness. In spite of the progresses, conventional therapies do not ensure long-term survival [1]. The NHL patients, who have a poor life expectation, could take advantage from innovative therapeutic strategies, such as immunotherapy. Specific antibodies can preferentially bind tumour cells over normal tissues. This specificity is based upon characteristics (surface antigens) that are completely independent from the parameters that allow for differential toxicity of chemo-and radiotherapy. The vascular nature of most lymphomas and their antigen expression make these tumours a favourable setting for treatment with monoclonal antibodies. In fact, the first successful use of antibodies as treatments for cancer was demonstrated in NHLs [2,3]. CD20 has been largely exploited as target antigen for immunotherapy with antibodies because it is expressed at high levels on B-lymphoma cells and is not expressed on stem c...