Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs.
Antibodies, Monoclonal ; chemistry ; Antibody Specificity ; Binding Sites, Antibody ; Immunoconjugates ; chemistry

Development of luminex-based solid phase assays enables advanced measurement of HLA antibody with sensitivity, specificity, and increasing knowledge of unacceptable antigens. In this review, we described the principle of the luminex-based assay and its current applications for organ transplantation including C1q assay, calculated panel reactive antibody, and virtual cross-matching. We also discussed the technical aspects and limitations for clinical utilization. The variables related to measurement of HLA antibody specificities and their clinical relevance remain unclear, therefore the interpretation of results requires comprehensive knowledge and clinical information in critical cases.
Antibody Specificity ; Immunoassay* ; Organ Transplantation* ; Sensitivity and Specificity ; Transplantation ; Transplants*

BACKGROUND: Determination of antibody specificity using antigram spread sheet requires experience and knowledge on in vitro characteristics of red cell antibodies, time-consuming, and still subjective to human error. A computer-based antibody identification system was developed to overcome these disadvantages. METHODS: Decision support system program for antibody identification was designed using Visual Basic 5.0 for Dade Data-cyte Plus. This system integrates the reaction patterns of saline, 37degrees C albumin, antiglobulin, 4degrees C saline enzyme treated and user-defined phases and lists the antibodies according to the probability. 115 irregular antibodies previously confirmed by standard manual method reanalyzed with this program. RESULTS: In 111 of 115 cases (96.5%), this system produced the same results with the manual identification. In two cases, of not matched 4 cases the computer program suggested additional antibodies and in one case, the computer program detected previous human error. In the other case, antibody identification was possible only after further tests including selective adsorption of multiple antibodies. CONCLUSION: The decision support system was rapid and easy and showed good concordance rate when compared with manual antibody identificaion results. In addition, human error could be reduced. Decision support system for antibody identification could be used in small blood banks by less experienced staffs.
Adsorption ; Antibodies ; Antibody Specificity ; Blood Banks ; Expert Systems ; Humans

BACKGROUND: HLA antisera are procured mainly from placental blood or blood of multiparous women. The latter has a merit that a large volume of antisera could be obtained, once the antisera are found to be of good quality. METHODS: A total of 1,437 multiparous blood donors were screened for the presence of anti- HLA antibodies. After the first screening with 20 panel cells, initially reactive sera were re- screened with 30 panel cells. RESULTS: Of 1,437 sera, 50 sera (3.5%) were reactive to both the first and the second screening panel cells. Among 50 sera, 25 (50.0%) sera could be assigned for their antibody specificity with r value of 0.8 or more. Only 14 samples (1.0%) showed reactivity to two or more panels with same antigen specificity and strength index of 80% or more. Four donors repeatedly donated blood with specificities of A24, A26, B7, and B7+B40, respectively. CONCLUSIONS: Screening of HLA class I antibodies in multiparous blood donors showed that HLA antisera of good quality could be obtained in about 1% of the donors in Korea.
Antibodies ; Antibody Specificity ; Blood Donors* ; Female ; Humans ; Immune Sera* ; Korea ; Mass Screening ; Sensitivity and Specificity ; Tissue Donors

BACKGROUND: The Rh system is the most important blood group after ABO in the transfusion field. Nearly half of irregular antibodies with specificity are related to Rh antigens in Korea. Formation of alloantibody for red blood cells is considered variable according to Rh phenotype of patients. We therefore studied the significance of Rh phenotype in Korean irregular antibody positive patients. METHODS: We performed retrospective reviews for the results of antibody identification tests performed from Jun. 2004 to Nov. 2013 in our university medical center. Rh phenotype, direct antiglobulin test, and antibody specificity were investigated. Rh phenotype was tested using RhD+ phenotype ID-card (DiaMed GmBH, Switzerland). RESULTS: A total of 504 patients were included. Of 504 patients, 495 (98.2%) were RhD positive. The proportion of Rh phenotype differed significantly between irregular antibody positive patients and known RhD positive Korean population in CDe phenotype (59.0% vs 39.4%, P<0.0001) and CcDEe phenotype (22.6% vs 38.4%, P<0.0001), respectively. The percentage of other Rh phenotype was not different in two groups. Formation of anti-E antibody in E negative patients was significantly higher than that of anti-C formation in C negative patients (P<0.0001). Sixteen patients showed antibodies with specificity for their own Rh system antigens. CONCLUSION: A significant disproportion of Rh phenotype was observed between irregular antibody positive patients and RhD positive Korean population. There would be a difference of immunogenicity among C/c and E/e antigens. E antigen matching might be considered first for patient required chronic transfusion if additional RBC matching would be implemented.
Academic Medical Centers ; Antibodies ; Antibody Specificity ; Coombs Test ; Erythrocytes ; Humans ; Korea ; Phenotype* ; Retrospective Studies ; Sensitivity and Specificity

Antibodies are immunoglobulins specifically introduced by immunity response of high animals, with the responsibility for recognising and cleaning out specific antigens. Antibody is not only a powerful weapon against pathogen invasion in the organism, but also a tool for specific molecular recognition used in basic scientific research. The diversity of antibody molecules resulted in the concept of antibody library; each individual animal is a natural antibody library. In the post-genome era, in order to fit various "omics", especially for proteomics requirement of high throughput technology, some gene engineering antibody libraries and antibody alternative libraries have been constructed based on phage display technology. Yet, more and more in vitro display systems such as ribosome display, mRNA display have been used for antibody library study, and that present more advantages than phage display. This mini review outlines the genesis, development and application prospect of antibody libraries according to the published reviews and research articles, and offers up to date development and application prospect of antibody library technology.
Animals ; Antibodies ; genetics ; physiology ; Antibody Diversity ; genetics ; Antibody Specificity ; Combinatorial Chemistry Techniques ; Gene Library ; Humans ; Peptide Library

Antibodies to high-incidence red blood cell antigens should be considered if panagglutination reactions are noted in all panel cells, and negative reactions to autologous red blood cells are detected on antibody screening and identification tests. In Korea, most of those antibodies are identified through international reference laboratories. To prevent a hemolytic transfusion reaction, antigen-negative red cells should be provided for those patients who have antibodies to red cell antigens. However, this is nearly impossible when the antibody has specificity to high-incidence red cell antigen. In those cases, transfusion of autologous blood, cryopreserved rare blood and the least incompatible blood components can be considered. In the case of surgery, acute normovolemic hemodilution or intraoperative blood salvage can also be considered. For the patients who have antibodies to high-incidence red cell antigens, it should be discussed to set up a national reference laboratory to quickly identify antibody specificities, and to consider establishing rare blood donor registry and frozen rare blood storage/supply system. This article reviews characteristics of antibodies to high-incidence antigens found in Koreans and also the transfusion experiences of those patients based on literature.
Antibodies ; Antibody Specificity ; Blood Donors ; Erythrocytes ; Hemodilution ; Humans ; Isoantibodies ; Korea ; Mass Screening ; Operative Blood Salvage ; Sensitivity and Specificity ; Transfusion Reaction

BACKGROUND: Panel reactive antibody (PRA) test is used to determine whether a patient awaiting transplantation is previously sensitized. Tail analysis algorithm is widely used to identify antibody specificities, but it is very difficult to perform manually. METHODS: To develop a web-based program, PHP (5.1.2), Apache (2.0.55), and MySQL (5.0.22) were used. Tail analysis algorithm was applied to identify specificities, which analyzed statistically 2 x 2 tables representing reactivities to broad antigens, splits and cross reactive groups (CREG). Exploiting two CREG classifications of Rodey (R) and Takemoto (T), antibody specificities were identified by 3 methods (ABC, R-ABC, T-ABC) simultaneously. Performance of the system was evaluated using 159 samples that showed > or =6 PRA% by a lymphocytotoxicity assay. RESULTS: A web-based system that can identify HLA antibody specificities was implemented on www.koreanhla.com. Among 159 samples tested, antibody specificities were identified in 151 (95.0 %), but not in 8 samples with PRA >97%. Among the 151 samples, 110 showed broad or split specificities and 41 CREG specificities. CONCLUSIONS: We developed a web-based computer program for the identification of HLA antibody specificities. Accessible to everyone on the internet, this program should be of help in sharing PRA results among laboratories.
Algorithms ; *Antibody Specificity/genetics ; HLA Antigens/genetics/*immunology ; Histocompatibility Testing ; Humans ; Internet ; *Software

BACKGROUND: It is recommended that ABO, Rh typing and unexpected antibody screening should be tested during pregnancy in order to prevent hemolytic disease of the newborn (HDN). However, it is unclear that a routine prenatal antibody screening test predicts the occurrence of HDN. We performed a retrospective study to determine the frequency of unexpected antibody during pregnancy, antibody specificity, and the usefulness of prenatal antibody screening as a predictor of HDN. METHODS: All 6,293 prenatal antibody screening were tested at Eulji hospital from April 1997 to December 2002. The results of antibody screening and identification test were reviewed in laboratory sheet. The past transfusion and pregnant history and postnatal HDN evidence were reviewed in pregnant women with positive antibody screening. A commercial two cell panel, Selectogen I, II, and panel cell (Ortho Diagnostic Systems Inc., Raritan, USA) were used with tube method until March 1999. In April 1999, reagent cells were changed to a gel agglutination test with ID-Diacell I, II and ID-Dia Panel of DiaMed-ID Micro Typing System (DiaMed AG, Cressier, Switzerland). RESULTS: Positive results of antibody screening test were found in 52 cases (0.83%, 52/6,293). Only 28 cases of them were tested antibody identification. Antibody specificity was identified at 22 cases and 17 (77.3%, 17/22) women had unexpected antibodies which are not associated with HDN. They were 11 with anti-Lea , 3 with anti-Leb, and 3 with anti-P1. The others were 3 cases of anti-E, 1 of anti-M, and 1 of anti-S. However, no one had evidence of HDN. CONCLUSION: These results suggest that routine prenatal antibody screening may not be necessary for all pregnant women except Rh (D) negative women or those who have a history of HDN.
Agglutination Tests ; Antibodies ; Antibody Specificity ; Female ; Humans ; Infant, Newborn ; Mass Screening* ; Pregnancy ; Pregnant Women ; Retrospective Studies

The ultimate goal of blood donor screening for anti-hepatitis C virus(HCV) antibodies is the specific exclusion of vital carriers from the blood donor population. Recently, a third-generation anti-HCV screening (Lucky HCD 3.0) and immunoblot assay (Lucky Confirm) using antigens derived from the core and different nonstructural regioris (NS3, NS4 and NS5) of the HCV vital genome were developed. To evaluate the usefulness of these assays, anti-HCV reaction patterns of the RIBA-2 and the presence of HCV-RNA detected by reverse transcriptase-polymerase chain reaction(RT-PCR) were examined in 180 sera, which were repeatedly positive in Abbott EIA-2, and HCV seroconversion panel sera. The reaction intensity of HCD 3.0 was higher than that of HCD 2.0. The sensitivity and positive predictive value for vital carrier state of HCD 3.0 were 98.4% and 85.4%, respectively. HCD 3.0 assay enabled the detection of the antibody response 2 weeks earlier than did other second-generation EIAs. RT-PCR testing of sera with RIBA-2-indetermihate results showed that 33.3%(10/30) had evidence of HCV-RNA. However, all of nine Lucky Confirm-indeterminate cases were negative for HCV-RNA. The sensitivity and specificity of Lucky Confirm test were 99.2% and 76.4%, respectively, and the positive and negative predictive values were 90.5% and 97.7%, respectively.
Antibodies ; Antibody Formation ; Blood Donors ; Carrier State ; Genome ; Humans ; Immunoenzyme Techniques* ; Mass Screening ; Sensitivity and Specificity