Delivery of Interferons to Target Cells by Monoclonal Antibodies: Potential for the Specific Targeting of Other Lymphokines

1988 ◽  
pp. 333-339
Author(s):  
H. K. Hochkeppel ◽  
S. S. Alkan
Keyword(s):  
Monoclonal Antibodies ◽  
Target Cells ◽  
Specific Targeting

scholarly journals Antibody-based therapy of leukaemia

2009 ◽  
Vol 11 ◽  
Author(s):  
John C. Morris ◽  
Thomas A. Waldmann
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Gemtuzumab Ozogamicin ◽  
Cell Leukaemia ◽  
Target Cells ◽  
Immune Effector ◽  
Effector Cells ◽  
Prolymphocytic Leukaemia ◽  
Immune Effector Cells

Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies – the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab – are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.

Monoclonal antibodies in cancer therapy.

1983 ◽  
Vol 1 (9) ◽  
pp. 582-590 ◽  
Author(s):  
R K Oldham
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Cancer Therapy ◽  
Experimental Approach ◽  
Preliminary Evidence ◽  
Current Status ◽  
Experimental Animals ◽  
Specific Targeting ◽  
Specific Tumor

The need for improved specificity in cancer therapy is apparent. With the advent of monoclonal antibodies, the possibility of specifically targeted therapy is being considered. Early trials of monoclonal antibody in experimental animals and humans have indicated its ability to traffic to specific tumor sites and to localize on or around the tumor cells displaying antigens to which the antibody is directed. This evidence of specific targeting, along with preliminary evidence of therapeutic efficacy for monoclonal antibodies and immunoconjugates with drugs, toxins, and isotopes is encouraging. The current status of clinical trials with monoclonal antibodies is reviewed and an example of the experimental approach for the development of immunoconjugates in animal models is presented.

Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION–cmHsp70.1)

Nanoscale ◽  
2015 ◽  
Vol 7 (48) ◽  
pp. 20652-20664 ◽  
Author(s):  
Maxim A. Shevtsov ◽  
Boris P. Nikolaev ◽  
Vyacheslav A. Ryzhov ◽  
Ludmila Y. Yakovleva ◽  
Yaroslav Y. Marchenko ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Iron Oxide ◽  
Ionizing Radiation ◽  
Iron Oxide Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Specific Targeting

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 Achieving dendritic cell subset-specific targeting in vivo by site-directed conjugation of targeting antibodies to nanocarriers

2021 ◽  
Author(s):  
Johanna Simon ◽  
Michael Fichter ◽  
Gabor Kuhn ◽  
Maxmimilian Brueckner ◽  
Cinja Kappel ◽  
...  
Keyword(s):  
Surface Functionalization ◽  
Targeted Delivery ◽  
Immune Cell ◽  
Specific Interaction ◽  
Cell Subset ◽  
Target Cells ◽  
Dendritic Cell Subset ◽  
Specific Targeting ◽  
Body Distribution

The major challenge of nanocarrier-based anti-cancer vaccination approaches is the targeted delivery of antigens and immunostimulatory agents to cells of interest, such as specific subtypes of dendritic cells (DCs), in order to induce robust antigen-specific anti-tumor responses. An undirected cell and body distribution of nanocarriers can lead to unwanted delivery to other immune cell types like macrophages reducing the vaccine efficacy. An often-used approach to overcome this issue is the surface functionalization of nanocarriers with targeting moieties, such as antibodies, mediating cell type-specific interaction. Numerous studies could successfully prove the targeting efficiency of antibody-conjugated carrier systems in vitro, however, most of them failed when targeting DCs in vivo that is partly due to cells of the reticuloendothelial system unspecifically clearing nanocarriers from the blood stream via Fc receptor ligation. Therefore, this study shows a surface functionalization strategy to site-specifically attach antibodies in an orientated direction onto the nanocarrier surface. Different DC-targeting antibodies, such as anti-CD11c, anti-CLEC9A, anti-DEC205 and anti-XCR1, were conjugated to the nanocarrier surface at their Fc domains. Anti-mouse CD11c antibody-conjugated nanocarriers specifically accumulated in the targeted organ (spleen) over time. Additionally, antibodies against CD11c and CLEC9A proved to specifically direct nanocarriers to the targeted DC subtype, conventional DCs type 1. In conclusion, site-directed antibody conjugation to nanocarriers is essential in order to avoid unspecific uptake by non-target cells while achieving antibody-specific targeting of DC subsets. This novel conjugation technique paves the way for the development of antibody-functionalized nanocarriers for DC-based vaccination approaches in the field of cancer immunotherapy.

AN IMPORTANT ROLE OF CARBOHYDRATE MOIETIES ON CANCER CELL MEMBRANE GLYCOPROTEINS IN CANCER CELL-INDUCED PLATELET AGGREGATION

1987 ◽  
Author(s):  
H Kitagawa ◽  
N Yamamoto ◽  
G Kosaki ◽  
H Yamazaki
Keyword(s):  
Monoclonal Antibodies ◽  
Platelet Aggregation ◽  
Cell Membrane ◽  
Western Blot ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Target Cells ◽  
Membrane Glycoproteins ◽  
Induced Aggregation

Platelet aggregation induced by cancer cells may be an essential process in the development of hematogenous metastasis of cancers. A mechanism in HMV-I (human vaginal melanoma cell line)-induced platelet aggregation was studied by using monoclonal antibodies against membrane proteins of cancer cells or platelets. HMV-I cells or their membrana ractions induced platelet aggregation of human heparinized PRP, to which hirudin had no inhibitory effect. The platelet aggregation by HMV-I was completely lost after the pretreatment of the cells with 0.3U/ml neuraminidase for 60 min at 37°C. Preincubation of platelets with monoclonal antibodies against platelet GP lb or GP Ilb/lIIa inhibited HMV-I induced aggregation. A monoclonal antibody MB3 (igM) against another human melanoma (HMMB) which had been transplanted in nude mice was produced by hybridoma technique. Screening studies by cell binding ELISA revealed that MB3 antibody reacted with not only HMMB cells but also many other cells including HMV-I, M7609 (colon carcinoma cell line) and normal fibroblasts. Western-blot analyses showedthat MB3 antibody reacted with multiple, more than ten, proteins with molecular weights ranging from UO to 200 kDa in unreduced SDS-PAGE of HMV-I, HMMB or M7609. In contrast, when .these cells pretreated with neuraminidase were used in Western-blot, MB3 reactivity were all lost. MB3 reacted with at least three glycoproteins of human red cell membrane in Western-blot, but it did not react with human platelets. Immune adherent asgay with trypsin-treated HMV-I or HMMB cells as target cells showed negative reactivity. MB3 antibody inhibited HMV-I-induced aggregation of platelets, but did not inhibit M7609-induced aggregation which depended on thrombin generation.These results suggest that MB3 antibody may be against sialic acid-containing carbohydrate moieties of membrane glycoproteins on these cancercells and that the carbohydrate(s) may play a critical role in' cancer cell-platelet interaction.

Costimulatory Effects of Interleukin-18 (IL-18) on Human Natural Killer (NK) Cells Activated through Fc Receptors for Immunoglobulin (IgG)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2780-2780
Author(s):  
Shivani Srivastava ◽  
Hailin Feng ◽  
Menggang Yu ◽  
David Pelloso ◽  
Michael Robertson
Keyword(s):  
Monoclonal Antibodies ◽  
Nk Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Conflicts Of Interest ◽  
Fc Receptors ◽  
Cytolytic Activity ◽  
Mitogen Activated Protein Kinase ◽  
Target Cells

Abstract Abstract 2780 NK cells play an important role in innate and adaptive immune responses. Most human NK cells express CD16, an Fc receptor for IgG that mediates lysis of antibody-coated target cells and costimulates interferon (IFN)-g production in response to cytokines. IL-18 is an immunostimulatory cytokine with antitumor activity in preclinical animal models. The effects of IL-18 on human NK cell function were examined. Here we show that NK cells stimulated with immobilized IgG in vitro secreted IFN-g; such IFN-g production was partially inhibited by blocking CD16 with monoclonal antibodies. IL-18 augmented IFN-g production by NK cells stimulated with immobilized IgG or CD16 antibodies (Figure 1). NK cell IFN-g production in response to immobilized IgG and/or IL-18 was inhibited by chemical inhibitors of Syk, extracellular signal-related kinases (ERK), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3-K). Stimulation with IL-18 or immobilized IgG could augment IL-12-induced IFN-g production by STAT4-deficient lymphocytes obtained from lymphoma patients after autologous stem cell transplantation (Figure 2). IL-18 also augmented the in vitro lysis of rituximab-coated Raji cells by human NK cells (Figure 3). These observations that IL-18 can co stimulate IFN-g production and cytolytic activity of NK cells activated through Fc receptors makes it an attractive cytokine to combine with monoclonal antibodies for treatment of cancer. Disclosure: No relevant conflicts of interest to declare.

Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells

Nature ◽  
1984 ◽  
Vol 307 (5953) ◽  
pp. 745-747 ◽  
Author(s):  
W. J. King ◽  
G. L. Greene
Keyword(s):  
Monoclonal Antibodies ◽  
Oestrogen Receptor ◽  
Target Cells

Immunotoxins containing saporin 6 and monoclonal antibodies recognizing plasma cell-associated antigens: Effects on target cells and on normal myeloid precursors (CFU-GM)

2009 ◽  
Vol 42 (3) ◽  
pp. 238-245 ◽  
Author(s):  
Luigi Barbieri ◽  
Angelo Dinota ◽  
Marco Gobbi ◽  
Pier Luigi Tazzari ◽  
Simonetta Rizzi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Cell ◽  
Target Cells
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