Abstract
Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.
Keywords: Anti-tumor immune response, calreticulin, heat shock proteins, HMGB1, HPMA-based doxorubicin delivery, targeted cytotoxic drugs.
Current Medicinal Chemistry
Title:HPMA Copolymer-Bound Doxorubicin Induces Immunogenic Tumor Cell Death
Volume: 20 Issue: 38
Author(s): M. Sirova, M. Kabesova, L. Kovar, T. Etrych, J. Strohalm, K. Ulbrich and B. Rihova
Affiliation:
Keywords: Anti-tumor immune response, calreticulin, heat shock proteins, HMGB1, HPMA-based doxorubicin delivery, targeted cytotoxic drugs.
Abstract: Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.
Export Options
About this article
Cite this article as:
Sirova M., Kabesova M., Kovar L., Etrych T., Strohalm J., Ulbrich K. and Rihova B., HPMA Copolymer-Bound Doxorubicin Induces Immunogenic Tumor Cell Death, Current Medicinal Chemistry 2013; 20 (38) . https://dx.doi.org/10.2174/09298673113206660281
DOI https://dx.doi.org/10.2174/09298673113206660281 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Molecular Treatment of Different Breast Cancers
Anti-Cancer Agents in Medicinal Chemistry Crosstalk Signalling Role in Modulation of Drugs Side Effects
Current Molecular Pharmacology Sunitinib in the Treatment of Thyroid Cancer
Current Medicinal Chemistry Bioengineering RNA Silencing Across the Life Kingdoms
Recent Patents on Biotechnology Antimicrobial Peptides in Oral Cancer
Current Pharmaceutical Design Natural Products as Anticancer Agents
Current Drug Targets Gene Electrotransfer: A Mechanistic Perspective
Current Gene Therapy Effects and Role of Multikinase Inhibitors in Thyroid Cancer
Current Pharmaceutical Design A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Anti-Cancer Agents in Medicinal Chemistry Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide Family: A Route Map towards Novel Drug Development
Current Molecular Pharmacology Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Spirocyclic Nucleosides in Medicinal Chemistry: An Overview
Mini-Reviews in Medicinal Chemistry Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier
Current Pharmaceutical Design Adverse Dermatological Reactions in Rheumatoid Arthritis Patients Treated with Etanercept, an Anti-TNFα Drug
Current Drug Safety Commercially Available, FDA-approved Epigenetic Modifiers As Therapeutic Agents in Bacterial Infection
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) Targeting of Cancer-Related Proteins with PNA Oligomers
Current Cancer Drug Targets Natural Products Based Anticancer Agents
Mini-Reviews in Organic Chemistry ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development
Current Pharmaceutical Design Macromolecular Drug Targets in Cancer Treatment and Thiosemicarbazides as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Xenobiotic Sulphation and its Variability During Inflammation: a Factor in Adverse Drug Reactions?
Current Drug Metabolism