Review: Highly Selective Compounds for the Antibody-Directed Enzyme Prodrug Therapy of Cancer

2003 ◽  
Vol 56 (9) ◽  
pp. 841 ◽  
Author(s):  
Lutz F. Tietze ◽  
Tim Feuerstein
Keyword(s):  
Monoclonal Antibody ◽  
Malignant Cells ◽  
High Potency ◽  
Selective Treatment ◽  
Enzyme Prodrug Therapy ◽  
Ic50 Value ◽  
Tumour Associated Antigens ◽  
Cytotoxic Compounds

Antibody-directed enzyme prodrug therapy (ADEPT) is a recent development for a selective treatment of cancer, based on site-directed formation at the surface of malignant cells of cytotoxic compounds from non-toxic prodrugs with a conjugate of an appropriate enzyme and a monoclonal antibody which binds to tumour-associated antigens. New potent prodrugs of analogues of the antibiotic CC-1065 have been developed. These show a remarkable selectivity with a Q(IC50) value of up to more than 3000. Moreover, the formed drug has a high potency with an IC50 of 30 pM.

Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer

2020 ◽  
Vol 20 (16) ◽  
pp. 1895-1907
Author(s):  
Navgeet Kaur ◽  
Anju Goyal ◽  
Rakesh K. Sindhu
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Therapeutic Agent ◽  
Hematologic Malignancies ◽  
Immune Checkpoints ◽  
Malignant Cells ◽  
Main Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Cancerous Cells

The importance of monoclonal antibodies in oncology has increased drastically following the discovery of Milstein and Kohler. Since the first approval of the monoclonal antibody, i.e. Rituximab in 1997 by the FDA, there was a decline in further applications but this number has significantly increased over the last three decades for various therapeutic applications due to the lesser side effects in comparison to the traditional chemotherapy methods. Presently, numerous monoclonal antibodies have been approved and many are in queue for approval as a strong therapeutic agent for treating hematologic malignancies and solid tumors. The main target checkpoints for the monoclonal antibodies against cancer cells include EGFR, VEGF, CD and tyrosine kinase which are overexpressed in malignant cells. Other immune checkpoints like CTLA-4, PD-1 and PD-1 receptors targeted by the recently developed antibodies increase the capability of the immune system in destroying the cancerous cells. Here, in this review, the mechanism of action, uses and target points of the approved mAbs against cancer have been summarized.

scholarly journals A new monoclonal antibody (CH-F42) recognizes a CD7- subset of normal T lymphocytes and circulating malignant cells in adult T-cell lymphoma- leukemia and Sezary syndrome

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1361-1368
Author(s):  
WB Labastide ◽  
MT Rana ◽  
CR Barker
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
Malignant Cells ◽  
Activation Markers ◽  
Normal Peripheral Blood

We describe a new rat immunoglobulin M monoclonal antibody (CH-F42) that recognizes a subset (1.5% to 8%) of normal peripheral blood T lymphocytes. The phenotype of these cells was determined, using dual- color immunofluorescence, to be CD2+, CD3+, CD4+, CD5+, CD7-, CD8-. They do not express T-cell activation markers, and are positive for UCHL1 (CD45RO), but negative for 2H4 (CD45RA). The antigen was expressed on circulating malignant cells in Sezary syndrome (four of four cases) and adult T-cell lymphoma-leukemia (ATLL) (four of six cases) and negative in a variety of other hematologic malignancies tested. These included chronic and acute lymphoid leukemias of B and T lineage, together with chronic and acute myeloid leukemias. However, normal CH-F42+ cells do not display any of the ultrastructural features associated with Sezary or ATLL cells. The marked similarities between these conditions together with the shared expression of an otherwise very restricted surface antigen (CH-F42) provide strong evidence for the existence of a common normal counterpart. Preliminary characterization studies of the antigen, which is also expressed by K562 and Jurkat cells, suggest the CH-F42 antigen is an O-linked, sialated glycan on a glycoprotein.

scholarly journals Effect of Monoclonal Antibodies Conjugation With Gallium-Containing Solamargine: Warburg Effect- Based Cancer Therapeutic Strategy. Article Review

2021 ◽  
pp. 47-59
Author(s):  
Waleed O. Atta
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Therapeutic Strategy ◽  
Aerobic Glycolysis ◽  
Malignant Cells ◽  
Long Time ◽  
High Degree

Therapy by Monoclonal antibodies is considered extremely hoping method for cancer therapy. But cancer cells have variable methods for resistance by multiple genetic mutations. The aim of that article to illustrate tagging monoclonal antibodies by gallium containing solamargine glycoside within the antibody by glycosylation the asparagine of its Fc portion. Malignant cells need to a big extent high carbohydrate content for aerobic glycolysis for cancer progression. Solamargine as a specific glycoside can be diffused easily and effectively into malignant cells with a high degree of specificity. Complexion gallium to solamargine then conjugation into monoclonal antibodies will increase Monoclonal antibody potency and affinity by Warburg effect based mechanism and gallium particles. Gallium can be retained for a long time inside malignant cells. By that method, the monoclonal antibody will be targeted to cancer cells by solamargine, retained gallium particles besides its functioning specific Fab region.

Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms

2020 ◽  
Vol 20 (8) ◽  
pp. 918-931
Author(s):  
Milad Ashrafizadeh ◽  
Reza Mohammadinejad ◽  
Saeed Samarghandian ◽  
Habib Yaribeygi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Side Effects ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Malignant Cell ◽  
Malignant Cells ◽  
High Potency ◽  
Cancer Management ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Proliferation And Metastasis

Cancer management and/or treatment require a comprehensive understanding of the molecular and signaling pathways involved. Recently, much attention has been directed to these molecular and signaling pathways, and it has been suggested that a number of biomolecules/players involved in such pathways, such as PI3K/Akt, NF-κB, STAT, and Nrf2 contribute to the progression, invasion, proliferation, and metastasis of malignant cells. Synthetic anti-tumor agents and chemotherapeutic drugs have been a mainstay in cancer therapy and are widely used to suppress the progression and, hopefully, halt the proliferation of malignant cells. However, these agents have some undesirable side-effects and, therefore, naturally-occurring compounds with high potency and fewer side-effects are now of great interest. Osthole is a plant-derived chemical compound that can inhibit the proliferation of malignant cells and provide potent anti-cancer effects in various tissues. Therefore, in this review, we presented the main findings concerning the potential anti-tumor effects of osthole and its derivatives and described possible molecular mechanisms by which osthole may suppress malignant cell proliferation in different tissues.

Development of Monoclonal Antibody Based Heterologous Immunoassay for Ractopamine Residue

2012 ◽  
Vol 461 ◽  
pp. 58-61
Author(s):  
Chao Ying Li ◽  
Jin Qing Jiang
Keyword(s):  
Monoclonal Antibody ◽  
Cell Fusion ◽  
Diglycidyl Ether ◽  
Fusion Technology ◽  
Mixed Anhydride ◽  
Animal Products ◽  
Coating Antigen ◽  
Standard Curve ◽  
Ic50 Value ◽  
Heterologous Icelisa

This study aimed to develop a monoclonal antibody based icELISA method for Ractopamine (Rac) residue. For this purpose, mixed anhydride method was employed to synthesize the immunogen of Rac-BSA and 1, 4-butanediol diglycidyl ether was used to prepare the coating antigen of Rac-OVA, thus pursue the heterologous sensitivity. Through cell fusion technology, four Hybridoma named R1-B5, R2-B3, R2-C6, and R4-C8 were screened out, and the Kas of all mAbs were between 2.7 and 4.8×109 L/mol. Based on the R1-B5 mAb, a heterologous icELISA standard curve was developed. The working range was from 0.013 to 33.7 ng/mL, with LOD and IC50 value of 0.007 ng/mL and 0.67 ng/mL, respectively. Therefore, this icELISA can be used for detecting Rac residue in animal products.

Proof of Principle in the Selective Treatment of Cancer by Antibody-Directed Enzyme Prodrug Therapy: The Development of a Highly Potent Prodrug

2002 ◽  
Vol 114 (5) ◽  
pp. 785-787 ◽  
Author(s):  
Lutz F. Tietze ◽  
Tim Feuerstein ◽  
Anja Fecher ◽  
Frank Haunert ◽  
Olaf Panknin ◽  
...  
Keyword(s):  
Selective Treatment ◽  
Enzyme Prodrug Therapy ◽  
Proof Of Principle

scholarly journals Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2472-2479 ◽  
Author(s):  
D Emilie ◽  
J Wijdenes ◽  
C Gisselbrecht ◽  
B Jarrousse ◽  
E Billaud ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Interleukin 6 ◽  
Clinical Symptoms ◽  
Large Cell ◽  
Malignant Cells ◽  
Protein Levels ◽  
Reactive Protein ◽  
Hodgkin's Lymphomas ◽  
Immunodeficiency Syndrome

Increased interleukin-6 (IL-6) production and expression by malignant cells of the IL-6 receptor has been evidenced in a subgroup of non- Hodgkin's lymphomas, suggesting that this cytokine plays a role in lymphoma growth and in B clinical symptoms. In this study, the effect of the administration of an anti-IL-6 monoclonal antibody (MoAb) was analyzed in 11 patients seropositive for human immunodeficiency virus-1 and suffering from an immunoblastic or a polymorphic large-cell lymphoma. The antibody (BE-8, 10 to 40 mg/day) was administered for 21 days. Neutralization of in vivo IL-6 effect was assessed by monitoring C-reactive protein levels in the serum. In 5 patients, the lymphoma progressed during treatment. Among them were the 2 patients in whom endogenous IL-6 effect was not neutralized. Five patients experienced a stabilization, and 1 a partial remission. This effect on lymphoma growth lasted for 8 to 28 weeks. The anti-IL-6 MoAb had a clear effect on lymphoma-associated fever and cachexia. The mean body weight increase was 1.4 +/- 0.5 kg between day 1 and day 21, and reached 12 kg in 120 days in 1 patient who received three courses of treatment. Side effects were a consistent but moderate thrombocytopenia, and an occasional and moderate decrease of neutrophil counts. Immunization against the MoAb was observed in only 2 patients. These results indicate that in some cases of lymphomas growth of malignant cells may be partially IL-6-dependent and that neutralizing endogenous effect of IL-6 completely abrogates B clinical symptoms.

Cytotoxic and Pro-apoptotic Activities of Diterpenoids from Zhumeria Majdae

2020 ◽  
Vol 17 ◽  
Author(s):  
Abolfazl Shakeri ◽  
Samira Navabi Nejad ◽  
Javad Asili ◽  
Milena Masullo ◽  
Mansoor Saeidi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cytotoxic Effect ◽  
Therapeutic Agent ◽  
2D Nmr ◽  
Etoac Extract ◽  
Chemical Structures ◽  
Ic50 Value ◽  
Cytotoxic Compounds ◽  
First Time ◽  
Mcf 7

Abstract:: Since the ethylacetate (EtOAc) extract of the roots of Zhumeria majdae had the potent cytotoxic effect (IC50 < 50 μg/ml) on three cancer cell lines; MCF-7, PC3 and MDA-MB-231, therefore the purpous of this study is to isolation of the responcible cytotoxic compounds from the plant. Isolation of the extract led to the identification of four diterpenoids named as lanugon Q (1), 12,16-dideoxy aegyptinone B (2), 12-deoxy-salvipisone (3) and manool (4). The chemical structures have been determined on the basis of 1D and 2D NMR experiments. Compound 1 is reported for the first time in the plants of Zhumeria genus. The results of cytotoxic and apoptotic evaluation revealed that compound 2 had the strong cytotoxic effect with the IC50 value of 15.90 μg/ml against MCF-7 cell lines. Sub-G1 peak in flow cytometry histogram of cells treated with EtOAc axtract and compound 2 showed the induction of apoptosis. Changes in the Bax/Bcl-2 ratio and cleavage of PARP were observed. It is to be noted that owing to strong cytotoxic effect, Z. majdae extract could be represented as therapeutic agent against cancer.

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