scholarly journals Taking the Hinge off: An Approach to Effector-Less Monoclonal Antibodies

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 50
Author(s):  
Jamie Valeich ◽  
Dan Boyd ◽  
Manu Kanwar ◽  
Daniel Stenzel ◽  
Deblina De Ghosh ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Domain Engineering ◽  
Target Antigen ◽  
Partial Recovery ◽  
Fc Gamma Receptors ◽  
Effector Functions ◽  
Diagnostic Applications ◽  
Hinge Domain

A variety of Fc domain engineering approaches for abrogating the effector functions of mAbs exists. To address some of the limitations of the current Fc domain silencing approaches, we are exploring a less commonly considered option which relies on the deletion of the hinge. Removal of the hinge domain in humanized IgG1 and IgG4 mAbs obliterates their ability to bind to activating human Fc gamma receptors I and IIIA, while leaving their ability to engage their target antigen intact. Deletion of the hinge also reduces binding to the Fc neonatal receptor, although Fc engineering allows partial recovery of affinity. Engineering of the CH3 domain, stabilizes hinge deleted IgG4s and prevents Fab arm exchange. The faster clearing properties together with the pacified Fc make modality of the hinge deleted mAb an appealing solution for therapeutic and diagnostic applications.

Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines

2005 ◽  
Vol 23 (26) ◽  
pp. 6421-6428 ◽  
Author(s):  
David G. Maloney
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Patient Specific ◽  
Chimeric Antibody ◽  
Target Antigen ◽  
Host Immune System ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.

scholarly journals Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head-and-neck cancer xenografts

2002 ◽  
Vol 99 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Iris Verel ◽  
Karl-Heinz Heider ◽  
Miranda Siegmund ◽  
El�nborg Ostermann ◽  
Erik Patzelt ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Nude Mice ◽  
Tumor Targeting ◽  
Target Antigen

Side-Effects of Monoclonal Antibody Infusions for the Diagnosis and Treatment of Cancer

1988 ◽  
Vol 3 (3) ◽  
pp. 147-153 ◽  
Author(s):  
E.F.H. van der Linden ◽  
M.J.P.G. van Kroonenburgh ◽  
E.K.J. Pauwels
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Side Effects ◽  
Diagnosis And Treatment ◽  
Target Cells ◽  
Clinical Use ◽  
Skin Reactions ◽  
Discontinuation Of Treatment ◽  
Diagnostic Applications ◽  
Toxic Reactions

This literature review presents an inventory of the nature and incidence of side-effects that arise from the clinical application of monoclonal antibodies (MoAb) for the diagnosis and treatment of cancer. Most side-effects occurred during therapy. Toxic reactions, such as fever, sweating and chills, were more common than immunological skin reactions; they were observed predominantly in association with the elimination of circulating target cells. Dosage and rate of administration of the MoAb appeared to have little influence on the reactions, which disappeared quickly and did not necessitate discontinuation of treatment. Serum sickness, anaphylactic reactions and bronchospasms were not common; the patients reacted quickly to the indicated therapy. Prevention of the side-effects described here, especially during diagnostic applications, was such that they need not form a barrier to the clinical use of MoAb.

scholarly journals Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Urai Chaisri ◽  
Wanpen Chaicumpa
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza A ◽  
Treatment Strategies ◽  
Passive Immunization ◽  
Single Chain ◽  
Effector Functions ◽  
Single Chain Antibodies ◽  
Therapeutic Monoclonal Antibodies

This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be producedin vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients) are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

Monoclonal antibodies in the diagnosis, detection and therapy of cancer

1982 ◽  
Vol 81 (4) ◽  
pp. 261-276
Author(s):  
R. W. Baldwin
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Mammary Carcinoma ◽  
Specific Antigen ◽  
Osteogenic Sarcoma ◽  
Blood Pool ◽  
Drug Conjugates ◽  
Human Lymphoblastoid Cell ◽  
Diagnostic Applications ◽  
Mouse Myeloma

SynopsisThe production of monoclonal antibodies specifying tumour associated antigens is illustrated by studies with a spontaneously arising rat mammary carcinoma (Sp4). Fusion of spleen cells from tumour-immune rats with mouse myeloma (P3NS1) yielded hybridomas secreting antibody reacting with a tumour specific antigen. These approaches have subsequently been used to produce monoclonal antibodies reacting with human osteogenic sarcoma, although in this case the antigens detected are tumour associated rather than tumour-specific.The diagnostic applications of these monoclonal antibodies have been explored particularly to evaluate whether radiolabelled preparations can be used for ‘imaging’ tumours. This approach has been validated with the human osteogenic sarcoma xenograft in tests showing that tumours can be detected by y-camera scanning following injection of 131I-labelled antibody when used in conjunction with blood pool labelling using 113MIn and a computerised subtraction technique.Monoclonal antibodies also have considerable potential for targetting drugs. These approaches are illustrated by studies using anti-rat mammary carcinoma Sp4 monoclonal antibody linked to adriamycin for therapy of subcutaneous tumour. In addition to drug conjugates, monoclonal antibodies are being used for targeting immunomodulating agents. This is illustrated by another series of studies in which the anti-human osteogenic sarcoma monoclonal antibody has been conjugated to human lymphoblastoid cell interferon to produce a reagent for activating host natural killer cells.

scholarly journals Monoclonal Antibodies Against LipL32, The Major Outer Membrane Protein of PathogenicLeptospira: Production, Characterization, and Testing in Diagnostic Applications

Hybridoma ◽  
2007 ◽  
Vol 26 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Cláudia P.H. Fernandes ◽  
Fabiana K. Seixas ◽  
Mariana L. Coutinho ◽  
Flávia A. Vasconcellos ◽  
Núbia Seyffert ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Major Outer Membrane Protein ◽  
Diagnostic Applications

Murine ascitic fluids contain varying amounts of an inhibitor that interferes with complement-mediated effector functions of monoclonal antibodies

1992 ◽  
Vol 33 (2) ◽  
pp. 135-138 ◽  
Author(s):  
B.J. Appelmelk ◽  
A.M.J.J. Verweij-Van Vught ◽  
J.J. Maaskant ◽  
L.G. Thijs ◽  
D.M. MacLaren
Keyword(s):  
Monoclonal Antibodies ◽  
Effector Functions

scholarly journals Evaluation of Diagnostic Applications of Monoclonal Antibodies against Avian Influenza H7 Viruses

2010 ◽  
Vol 17 (9) ◽  
pp. 1398-1406 ◽  
Author(s):  
Ming Yang ◽  
Alfonso Clavijo ◽  
Jill Graham ◽  
John Pasick ◽  
James Neufeld ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dot Blot ◽  
Western Blots ◽  
Positive Antibody ◽  
Dot Blot Assay ◽  
Diagnostic Applications ◽  
Ha Protein ◽  
H7 Subtype

ABSTRACT A panel of monoclonal antibodies (MAbs) was generated from mice immunized with binary ethylenimine (BEI)-inactivated H7N1 (A/TK/ON/18-2/00) virus. Using a dot blot assay, six of seven MAbs reacted with viruses of the H7 subtype, but not with any of the other 15 hemagglutinin (HA) subtypes tested. Four of the seven MAbs reacted with 14 different H7 isolates, indicating that the MAbs binding epitopes are conserved among viruses of the H7 subtype. The binding epitopes of all seven MAbs were conformational and reacted with the HA1 fraction of the HA protein in Western blots under nonreducing conditions. Applications of these MAbs in the development of rapid tests for H7 subtype viruses were evaluated. The MAbs demonstrated reactivity with AI virus H7 antigen in immunofluorescence and immunohistochemistry assays. Monoclonal antibody 3 showed a very strong immunostaining in the formalin-fixed and paraffin-embedded tissue from the H7N3 virus-infected chicken. A double-antibody sandwich (DAS) enzyme-linked immunosorbent assay (ELISA) was developed using two of the MAbs. The DAS ELISA specifically detected all H7 strains tested in this study. A competitive ELISA (cELISA) for the detection of H7-specific antibodies was evaluated using one MAb and BEI-inactivated H7N1 virus as the antigen. All infected birds showed positive antibody responses at 7 days postinfection. The sensitivity of this cELISA was comparable with that of an influenza A nucleoprotein-based cELISA. This panel of MAbs is valuable in the development of various immunoassays.

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