Doxorubicin-Conjugated Anti-Midkine Monoclonal Antibody as a Potential Anti-Tumor Drug

Abstract

The result raises the possibility of using anti-midkine antibody conjugated with DOX for cancer therapy.

Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

“…Pre-thiolation of immunoglobulin, F(ab') 2 , Fab, or other biological proteins is usually required due to the relatively low number of nonsterically hindered sulfhydryl groups in the form of reduced cysteine amino acid residues (e.g., R-SH) available within their amino acid sequence. Increasing the number of available reduced sulfhydryl groups can be achieved by the application of 1,4-dithiothreitol which reduces intramolecular cystine-cystine bonds 28,31,32 and similar disulfide structures 113 (DTT: R-CH 2 -S-S-CH 2 -R / 2 R-CH 2 -SH). The actual synthetic introduction of ''new'' or additional reduced sulfhydryl groups at the e-amine of lysine amino acid residues is possible with reactions that utilize 2-iminothiolane (2-IT), 2,6,26,30,114 mercaptosuccinimide, 115 or N-succinimidyl-S-acetylthioacetate (SATA).…”

“…Monoclonal immunoglobulin fractions are frequently utilized for specific recognition and physical binding to antigens or receptor complexes uniquely overexpressed on the exterior surface membrane of neoplastic cell populations. 7,[26][27][28][29][30] Doxorubicin 28,29,[31][32][33] has been the most common anthracycline to date utilized to synthesize covalent immunochemotherapeutics in addition to the relatively limited utilization of daunorubicin [34][35][36] and epirubicin.…”

“…Covalent anthracycline immunochemotherapeutics have been designed to selectively ''target'' chemotherapeutic delivery, and evoke potent ex vivo cytotoxic anti-neoplastic potency against several neoplastic cell types including mammary adenocarcinoma (anti-HER2/neu, anti-epidermal growth factor receptor [EGFR]), 7,26 colon adenocarcinoma (anti-CEA) 36 ; multiple myeloma (CD38 + , MC/CAR), 28 B-lymphoma, 32 melanoma, 27,29,35 gastric carcinoma, 39 colon carcinoma, 37 pulmonary carcinoma, 40 and other neoplastic cell types (CEA). 34,35 In direct accord with their level of in vitro efficacy, similar covalent anthracycline immunochemotherapeutics reduce in vivo tumor burden and prolong survival against human xenografts of gastric carcinoma, 39 breast cancer, 33 CD38 positive MC/CAR multiple myeloma, 28 B-lymphoma, 32 T-cell lymphoma, 41 colon carcinoma, 33,[42][43][44] ovarian carcinoma, 42 pulmonary carcinoma, 33 metastatic melanoma, 27,29 hepatocellular carcinoma, 31 and intracerebral small-cell lung carcinoma. [45][46][47] In part these findings correlate with the recognized additive and synergistic levels of cytotoxic anti-neoplastic potency of anti-HER2/neu (inhibited HER2/neu function) in concert with conventional chemotherapeutics such as cyclophosphamide, 48,49 docetaxel, 48 doxorubicin, 48,49 etoposide, 48 methotrexate, 48 paclitaxel, 48,...…”

siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization

“…Doxorubicin-conjugated anti-MK monoclonal antibody was reported as a potential anti-tumor drug [11]. Mouse MK antisense oligodeoxynucleotide demonstrated potent growth inhibitory effects on rectal carcinoma growth in vivo [12].…”

Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

“…One example is the use of hydrotropic magnetic micelles for combined magnetic resonance (MR) imaging and cancer treatment, [4][5][6] chemotherapy, 7 and targeting of hepatocytes using SPION-loaded chitosan-linoleic acid. 8 They can also be used for delivery of drugs such as doxorubicin, platinum compounds, anti-inflammatory drugs, and prodrugs.…”