Improved method for generation of HLA-DR allele specific monoclonal antibodies using phage libraries

1997 ◽  
Vol 56 (1-3) ◽  
pp. 375
Author(s):  
B Hansen
Keyword(s):  
Monoclonal Antibodies ◽  
Improved Method ◽  
Hla Dr ◽  
Allele Specific ◽  
Phage Libraries

Improved method for generation of HLA-DR allele specific monocional antibodies using phage libraries

1997 ◽  
Vol 56 ◽  
pp. 375
Author(s):  
B.E. Hansen ◽  
M.W. Hildinge ◽  
A. Svejgaard ◽  
J. Engberg ◽  
L. Fugger
Keyword(s):  
Improved Method ◽  
Hla Dr ◽  
Allele Specific ◽  
Phage Libraries

TUMOUR IMAGING USING AN IMPROVED METHOD OF DTPA-COUPLED MONOCLONAL ANTIBODIES RADIOLABELLED WITH METALLIC RADIONUCLIDES

The Lancet ◽  
1984 ◽  
Vol 324 (8395) ◽  
pp. 169 ◽  
Author(s):  
A.A. Epenetos ◽  
D. Snook ◽  
G. Hooker ◽  
J.P. Lavender ◽  
K.E. Halnan
Keyword(s):  
Monoclonal Antibodies ◽  
Tumour Imaging ◽  
Improved Method

scholarly journals Heterogeneity in a lymphoid tumor: coexpression of T and B surface markers

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 373-380 ◽  
Author(s):  
RW Schroff ◽  
KA Foon
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Progenitor Cell ◽  
Leukemic Cells ◽  
Cytotoxic T Cell ◽  
Surface Markers ◽  
Lymphoid Tumor ◽  
Surface Immunoglobulin ◽  
Hla Dr

Abstract Heterogeneity of leukemic cells was defined in a case of lymphoma. Four phenotypically distinct subpopulations of leukemic cells were identified. One subpopulation was observed to simultaneously express B- and T-cell characteristics. B-cell characteristics included monoclonal IgM (lambda) surface immunoglobulin, HLA-DR antigens, and expression of the B-cell antigen identified by the BA-1 monoclonal antibody. T-cell characteristics included E-rosette formation, expression of the pan-T- associated antigens recognized by the Leu-1 and OKT-11 monoclonal antibodies, and expression of the suppressor cytotoxic T-cell- associated antigen recognized by the Leu-2 and OKT-8 monoclonal antibodies. In addition to this subpopulation, three other phenotypically distinct subpopulations were identified, two of which expressed monoclonal IgM (lambda) surface immunoglobulin. The results of this investigation indicates that three phenotypically distinct lymphoid subpopulations bearing B-cell characteristics, and probably a fourth T-cell subgroup, were derived from a common lineage. These findings suggest that the malignancy involved a lymphoid progenitor cell that may possess diverse maturational capacity.

Human FcγRIII (CD16) Polymorphism Screening Is Enhanced with Pyrosequencing Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4911-4911
Author(s):  
Ksenia Matlawska-Wasowska ◽  
James Gale ◽  
Parisa Khalili ◽  
Bridget S Wilson ◽  
Mohammad Vasef ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Targeted Therapies ◽  
Nested Pcr ◽  
Immune Cell ◽  
Conflicts Of Interest ◽  
Therapeutic Potential ◽  
Allelic Polymorphism ◽  
Allele Specific ◽  
Specific Restriction

Abstract Abstract 4911 Surface specific antigens expressed on the cell membrane of hematopoietic cells are attractive target for antibody mediated cancer cells therapy. Monoclonal antibodies involve various mechanisms to eliminate cancer cells, including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) mediated by immune effector cells such as NK cells and macrophages bearing FcγRIIIA (CD16) receptor. Previous studies reported that clinical efficacy of monoclonal antibodies can be linked to the single nucleotide polymorphism found at position 559 in cDNA of the gene encoding FcγRIIIA. This allelic polymorphism generateses the following allotypes V/V, F/V or F/F at amino acid position 158 and can affect binding of mAbs and immune cell effector function. CD16-mediated binding is most efficient with the V/V genotype, and least efficient with the F/F genotype, leading to a range of efficacy in mAb-mediated targeted therapies. Currently, many patients are not screened for CD16 heterozygosity. Nevertheless there is a clear need for a diagnostic assay that will allow estimating the allelic polymorphism of a patient undergoing treatment with monoclonal antibodies utilizing ADCC/ADCP. Here we hypothesized that the pyrosequencing might improve a screening for polymorphisms of human FcγRIIIA-158 receptor. We studied 42 normal human subjects for the incidence of V/V, F/V and F/F CD16 polymorphisms using pyrosequencing technologies and compared to nested PCR-based allele-specific restriction assay. Compared to pyrosequencing, the nested PCR-based allele-specific restriction assay was 0. 33 sensitive and 1. 0 specific in discriminating the V/V and F/F genotypes, and 0. 33 sensitive and 0. 7 specific for the V/V and F/V genotypes (Table 1). Compared to pyrosequencing, the nested PCR-based allele-specific restriction assay was relatively insensitive and not specific in distinguishing the V/V genotype from other genotypes. Since the efficacy of the mAb-based targeted immunotherapy may be highly dependent upon the CD16 polymorphism in any given individual, we propose that pyrosequencing of the CD16 receptor be routinely evaluated in all patients. Such practices might prevent patients from randomizing to receive targeted therapies to that hematological malignancies for that have little or no therapeutic potential. Table 1 V/V F/V F/F pyrosequencing 6 16 20 allele-specific restriction assay 2 23 17 sensitivity - 0.33 0.33 specificity - 0.7 1.0 Disclosures: No relevant conflicts of interest to declare.

HLA-DR expression on monocytes as a prognostic criterion for the development of pyoinflammatory processes at various stages of surgical treatment

2016 ◽  
Vol 94 (5) ◽  
pp. 379-382
Author(s):  
Mariya V. Chepeleva
Keyword(s):  
Monoclonal Antibodies ◽  
Surgical Treatment ◽  
Periprosthetic Infection ◽  
Relative Content ◽  
Immune Disorders ◽  
Flow Cytofluorometry ◽  
Posttraumatic Osteomyelitis ◽  
Hla Dr ◽  
Prognostic Criterion ◽  
Tubular Bones

We studied relative content of CD14+HLA-DR in 214 patients including those with aseptic instability and stable implants of the knee and the hip, periprosthetic infection of the hip, chronic posttraumatic osteomyelitis of long tubular bones, and osteomyelitis generalization (sepsis). We determined HLA-DR expression on monocytes by laser flow cytofluorometry using Beckman Coulter Epics XL (USA) cytometer and monoclonal antibodies (Immunotech Company, France). It has been demonstrated, that the decrease in HLA-DR expression on monocytes can be one of the mechanisms of increasing immune disorders in patients with orthopedic pathology and monitoring HLA-DR monocytic expression can be used as a prognostic criterion of developing pyoinflammatory processes at the stages of surgical treatment.

scholarly journals Therapy of B-cell malignancies by anti–HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5180-5190 ◽  
Author(s):  
Rhona Stein ◽  
Pankaj Gupta ◽  
Xiaochuan Chen ◽  
Thomas M. Cardillo ◽  
Richard R. Furman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Kinase Signaling ◽  
Jnk Signaling ◽  
Multiple Myeloma Cell ◽  
Hla Dr

Abstract A humanized IgG4 anti–HLA-DR monoclonal antibody (IMMU-114), engineered to avoid side effects associated with complement activation, was examined for binding and cytotoxicity on leukemia, lymphoma, and multiple myeloma cell lines and chronic lymphocytic leukemia (CLL) patient specimens, followed by evaluation of the effects of IMMU-114 on extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. HLA-DR was expressed on the majority of these cells at markedly higher levels than CD20, CD22, and CD74. IMMU-114 was toxic to mantle cell lymphoma, CLL, acute lymphoblastic leukemia, hairy cell leukemia, non-Hodgkin lymphoma (including rituximab-resistant), and multiple myeloma cell lines, and also patient CLL cells. IMMU-114 induced disease-free survival in tumor-bearing SCID mice with early-stage disease and in models that are relatively resistant to anti-CD20 monoclonal antibodies. Despite positive staining, acute myelogenous leukemic cells were not killed by IMMU-114. The ability of IMMU-114 to induce activation of ERK and JNK signaling correlated with cytotoxicity and differentiates the mechanism of action of IMMU-114 from monoclonal antibodies against CD20 and CD74. Thus, antigen expression is not sufficient for cytotoxicity; antibody-induced hyperactivation of ERK and JNK mitogen activated protein kinase signaling pathways are also required.

Sign in / Sign up

Export Citation Format

Share Document