Cascade iodination: a novel method to enhance the safety and efficacy of therapeutic proteins

Abstract

administration of rituximab causes depletion of B cells expressing the surface antigen CD20. The mechanism of cell killing is thought to be secondary to antibody-dependent cellular toxicity and complement activation. Suppression of autoreactive B cells may explain the sustained response attained when using rituximab in the treatment of lymphomas and autoimmune disorders [3,4].In this report, four of five patients achieved durable remission confirming the successful outcome using rituximab in refractory TTP recently reported by other investigators [5][6][7]. The dose and frequency of administration of rituximab in the current series is based on the experience in the treatment of non-Hodgkin's lymphoma. The time to recovery of platelet counts in our patients is consistent with the results observed in patients with idiopathic thrombocytopenic purpura [4]. All patients in that study received rituximab in a dose and frequency similar to the current series.Because of the limited available experience in the treatment of TTP with rituximab, it is difficult to make direct comparison with the results obtained from other investigators [5][6][7]. For example, one patient with chronic relapsing TTP achieved a rather short remission with two doses and a sustained remission after four infusions of rituximab [6]. In another case, full recovery of platelet count and durable remission was achieved after only two doses of rituximab [5]. Therefore, the number of doses of rituximab required to achieve response in patients with refractory TTP is worth addressing in future trials. It is also important to emphasize that PLEX was used on a daily basis in our patients until platelet recovery. Unfortunately, no information is currently available on whether rituximab is removable by PLEX. As plasma levels of rituximab were not measured in this group of patients, it is difficult to assess the impact of PLEX on the efficacy of rituximab. As would be expected intuitively, durable remission correlated well with recovery of VWF-CPA and resolution of the inhibitor. The duration and type of treatment previously administered did not influence the response to rituximab in this study. However, it is important to note that the non-responder in our series had an underlying condition (malignancy) that typically does not respond well to PLEX and other therapeutic strategies.In summary, rituximab is potentially an effective and well tolerated agent in patients with refractory TTP. The frequency of infusion and sequence of administration, i.e. immediately after failure of PLEX or following splenectomy should be further investigated.

Is citrate deficiency universal?

“…Recently, my grandson Corey, a math major at the University of California Santa Cruz, was attempting to explain some exotic mathematics and showed me the opening sentences of Chapter 2 in his text book: ‘We have an intuitive concept of the real number system used by mathematicians since at least the period of ancient Greek mathematics.’ That gave me the courage in this age of ‘evidence‐based medicine’ [1] to intuitively conclude that much of our research in blood is either wrong or needs to be reevaluated. We discovered this during our work on ‘cascade iodination’, a method to inactivate pathogens in plasma proteins [2] which led to the concept of ‘supercryoprecipitate’ [3]. The original amount of anticoagulant used in transfusion was limited by the fact that higher amounts of citrate would damage the cellular portion of blood at a time when plasma elements were relatively unimportant.…”