RESUMO
A method to measure the antibody-dependent cell-mediated phagocytosis (ADCP) potency of anti-CD38 mAb was developed based on design of experiment (DoE) with a Jurkat/NFAT/CD32a-FcεRIγ transgenic cell line as the effector cell, the Daudi cell line as the target cells, and luciferase as the detection system. The DoE method was used for optimization of experimental parameters and methodological validation. The results show that anti-CD38 mAb exhibits a dose-response relationship with the following four-parameter equation: y = (A - D) / [1 + (x / C)B] + D. Several experimental parameters were optimized by statistical experimental design and determined as follows: the working concentration of anti-CD38 mAb was 800-20.81 ng·mL-1, the density of the target cells was 7.5×104 per well, and the density of effector cells was 2.5×104 per well, with an induction time of 6 h. The method showed good specificity. The recovery rate for samples from 5 different groups showed that the relative potencies of anti-CD38 mAb were (59.97 ± 4.74) %, (82.44 ± 5.15) %, (110.69 ± 11.71) %, (129.23 ± 5.22)% and (162.15 ± 3.66) %. The recoveries ranged from 103% to 120% and the RSDs of the above results were all less than 11%. The linear detection range was 50%-150%. Based on DoE design, this method for measuring ADCP potency of anti-CD38 mAb was optimized and validated with good specificity, repeatability and accuracy. This method can be used for evaluation of ADCP biological activity of anti-CD38 mAbs.
RESUMO
【Objective】 To explore the challenging blood cross-matching and resolution for multiple myeloma (MM) patients in different disease stages. 【Methods】 For a patient who was first diagnosed as MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method and tube test. When the major side of cross-matching was agglutinated, the patient’s plasma was cross matched with donors’ red blood cell (RBC) by polybrene test, then plasma dilution cross matched with donors’ RBC by microcolumn gel method. For a patient who was diagnosed as recurrent refractory MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method. 【Results】 1) Case 1 was a first-visit outpatient. The major side of microcolumn cross-match test was agglutinated with the shape of fine line. The result of tube method also showed agglutination of major sides, and the rouleaux were detected by the microscopy. Then polybrene method and microcolumn gel method (after plasma diluted) were applied for cross-matching again with the above two donors’ blood and showed compatibility. 2) Case 2 was a recurrent refractory MM patient. The major and minor sides of microcolumn cross-match test were both agglutinated with the shape of granular. The patient was treated with anti-CD38 monoclonal antibody. The RBCs, after treated with dithiothreitol (DTT) was used to cross match with patient plasma by microcolumn test, and the result was compatible. 【Conclusion】 Polybrene method and microcolumn gel method after plasma diluted are suitable for blood cross-matching of newly diagnosed MM patients, also for those treated with CD38 monoclonal antibody, as the drug interference with cross-matching can be eliminated by DTT.
RESUMO
【Objective】 To investigate the clinical feasibility of polybrene method to remove serological interference in patients receiving anti-CD38 monoclonal antibody for the treatment of multiple myeloma, and its detection performance of alloantibodies. 【Methods】 For patients receiving anti-CD38 monoclonal antibody for the treatment of multiple myeloma, unexpected antibody screening and cross-matching blood test were performed by polybrene method. 【Results】 The polybrene method can remove the interference of anti-CD38 monoclonal antibodies on blood group serology; both methods can effectively remove anti-CD38 monoclonal antibody to detect anti-E, anti-D, anti-Fya and anti-S antibodies.The titers of anti-D, anti-E, anti-Fya and anti-S alloantibodies, yielded by enhanced polybrene method, were higher than those of the polybrene method.Seven patients received K-antigen-negative blood transfusion without any adverse reactions to blood transfusion. 【Conclusion】 For the treatment of multiple myeloma using CD38 monoclonal antibody, the polybrene method can quickly and effectively remove the interference of daratumumab with blood group serology.
RESUMO
With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.
RESUMO
The treatments of multiple myeloma (MM) have been made remarkable progress in recent years,and especially in 2015,FDA approved a number of new drugs for treatment of relapsed and refractory MM.At the 21th European Hematology Association Annual Meeting,the issue of MM has received a lot of attention.The recent progress of MM in this conference will be briefly introduced in this review.