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Cell-Based Drug-Delivery Platforms

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 69334

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Special Issue Editors

Prof. Dr. José Martínez Lanao

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Guest Editor

1. Department of Pharmaceutical Sciences, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain
2. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Interests: drug delivery; cell carriers; nanoparticles; pharmacokinetics; anti-infectives; pharmaceutical development
Special Issues, Collections and Topics in MDPI journals

Dr. Carmen Gutierez-Millan

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Guest Editor

1. Department of Pharmaceutical Sciences, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain
2. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Interests: erythrocytes; drug delivery; cell-based platforms; nanoparticles; exosomes
Special Issues, Collections and Topics in MDPI journals

Dr. Clara Isabel Colino Gandarillas

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Guest Editor

1. Department of Pharmaceutical Sciences, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain
2. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Interests: controlled drug delivery; nanoparticles; cell-based drug delivery; antiinfective therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Within the framework of nanomedicine, drug delivery has experienced rapid progress in recent years. Delivery systems based on cells or their derivative products are interesting and promising alternatives to other nanosystems, such as nanoparticles. These systems can be applied in diverse therapeutic fields, such as cancer, cardiovascular therapeutics, anti-infective therapeutics or vaccines, among others.

Circulating cells such as erythrocytes, platelets, stem cells or dendritic cells may be used as drug delivery platforms. Autologous or heterologous erythrocytes have applications as circulating bioreactors, for controlled drug release or for the selective targeting of therapeutic substances to the reticuloendothelial system (RES). In addition, engineered platelets may be used for innovative cancer therapies based on the use of immunotherapeutic agents, such as monoclonal antibodies. Strategies based on the use of mesenchymal stem cells (MSC) for drug delivery are cancer chemotherapy, drug-loaded micro- or nanoparticles or immunotherapy, among others. In addition, antigen-presenting cells such as dendritic cells may be used for immunotherapeutic vaccines in hematologic cancer.

Bacterial ghosts from gram-negative bacteria obtained by E-mediated lysis have importance in immunotherapy for DNA-based animal vaccines or for the delivery of antineoplastic drugs in cancer cells.

Exosomes are extracellular vesicles from endocytic compartments of different types of eukaryotic cells that have applications as delivery systems of drugs and genetic material. Another promising approach is cell membrane coating nanotechnology. It is based on the use of membranes from different types of cells like erythrocytes, platelets, leukocytes, cancer, bacteria or stem cells to coat nanoparticles such as polymeric or metallic, among others, providing them biomimetic properties. These functionalized nanosytems have potential theranostic applications, especially in cancer therapy.

The purpose of this Special Issue is to present the most recent research in the field of delivery systems based on cells, modified cells, and derivative systems, and their therapeutic applications. The manuscripts to be included may present results of recent research or updated reviews of different topics related to the main goal of this issue.

This Special Issue will cover the following topics but is not limited to them:

Ghost erythrocytes as drug carriers of drugs and peptides;
Engineered platelets for tumor targeting of monoclonal antibodies;
Dendritic cells vaccines for hematologic malignancies;
Mesenchymal stem cells for drug delivery in cancer therapy;
Animal vaccines based on the use of bacterial ghosts;
Exosomes for drugs and gene delivery;
Cell-membrane coated nanosystems for drug delivery;
Cell-based drug delivery systems for gene therapy;
Cancer cell-based drug delivery platforms;
Industrial production of cell-based drug delivery system.

Prof. José Martínez Lanao
Dr. Carmen Gutiérrez
Dr. Clara I. Colino
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Cell-based drug delivery
Ghost erythrocytes
Engineered platelets
Dendritic cells
Mesenchymal stem cells (MSC)
Bacterial ghosts
Exosomes
Cell-membrane coating nanotechnology

Published Papers (13 papers)

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Editorial

Jump to: Research, Review

4 pages, 178 KiB

Open AccessEditorial

Cell-Based Drug Delivery Platforms

by José M. Lanao, Carmen Gutiérrez-Millán and Clara I. Colino

Pharmaceutics 2021, 13(1), 2; https://doi.org/10.3390/pharmaceutics13010002 - 22 Dec 2020

Cited by 9 | Viewed by 1894

Abstract

Within the framework of nanomedicine, drug delivery has experienced rapid progress in recent years [...] Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

Research

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15 pages, 1925 KiB

Open AccessArticle

Automated Large-Scale Production of Paclitaxel Loaded Mesenchymal Stromal Cells for Cell Therapy Applications

by Daniela Lisini, Sara Nava, Simona Frigerio, Simona Pogliani, Guido Maronati, Angela Marcianti, Valentina Coccè, Gianpietro Bondiolotti, Loredana Cavicchini, Francesca Paino, Francesco Petrella, Giulio Alessandri, Eugenio A. Parati and Augusto Pessina

Pharmaceutics 2020, 12(5), 411; https://doi.org/10.3390/pharmaceutics12050411 - 30 Apr 2020

Cited by 20 | Viewed by 3064

Abstract

Mesenchymal stromal cells (MSCs) prepared as advanced therapies medicinal products (ATMPs) have been widely used for the treatment of different diseases. The latest developments concern the possibility to use MSCs as carrier of molecules, including chemotherapeutic drugs. Taking advantage of their intrinsic homing feature, MSCs may improve drugs localization in the disease area. However, for cell therapy applications, a significant number of MSCs loaded with the drug is required. We here investigate the possibility to produce a large amount of Good Manufacturing Practice (GMP)-compliant MSCs loaded with the chemotherapeutic drug Paclitaxel (MSCs-PTX), using a closed bioreactor system. Cells were obtained starting from 13 adipose tissue lipoaspirates. All samples were characterized in terms of number/viability, morphology, growth kinetics, and immunophenotype. The ability of MSCs to internalize PTX as well as the antiproliferative activity of the MSCs-PTX in vitro was also assessed. The results demonstrate that our approach allows a large scale expansion of cells within a week; the MSCs-PTX, despite a different morphology from MSCs, displayed the typical features of MSCs in terms of viability, adhesion capacity, and phenotype. In addition, MSCs showed the ability to internalize PTX and finally to kill cancer cells, inhibiting the proliferation of tumor lines in vitro. In summary our results demonstrate for the first time that it is possible to obtain, in a short time, large amounts of MSCs loaded with PTX to be used in clinical trials for the treatment of patients with oncological diseases. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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14 pages, 4158 KiB

Open AccessArticle

Adipose-Derived Stem Cells Primed with Paclitaxel Inhibit Ovarian Cancer Spheroid Growth and Overcome Paclitaxel Resistance

by Cinzia Borghese, Naike Casagrande, Giuseppe Corona and Donatella Aldinucci

Pharmaceutics 2020, 12(5), 401; https://doi.org/10.3390/pharmaceutics12050401 - 27 Apr 2020

Cited by 17 | Viewed by 2805

Abstract

Adipose-derived stem cells (ADSCs) primed with paclitaxel (PTX) are now hypothesized to represent a potential Trojan horse to vehicle and deliver PTX into tumors. We analyzed the anticancer activity of PTX released by ADSCs primed with PTX (PTX-ADSCs) (~20 ng/mL) in a panel of ovarian cancer (OvCa) cells sensitive or resistant to PTX. We used two (2D) and three dimensional (3D) in vitro models (multicellular tumor spheroids, MCTSs, and heterospheroids) to mimic tumor growth in ascites. The coculture of OvCa cells with PTX-ADSCs inhibited cell viability in 2D models and in 3D heterospheroids (SKOV3-MCTSs plus PTX-ADSCs) and counteracted PTX-resistance in Kuramochi cells. The cytotoxic effects of free PTX and of equivalent amounts of PTX secreted in PTX-ADSC-conditioned medium (CM) were compared. PTX-ADSC-CM decreased OvCa cell proliferation, was more active than free PTX and counteracted PTX-resistance in Kuramochi cells (6.0-fold decrease in the IC50 values). Cells cultivated as 3D aggregated MCTSs were more resistant to PTX than 2D cultivation. PTX-ADSC-CM (equivalent-PTX) was more active than PTX in MCTSs and counteracted PTX-resistance in all cell lines. PTX-ADSC-CM also inhibited OvCa-MCTS dissemination on collagen-coated wells. In conclusion, PTX-ADSCs and PTX-MSCs-CM may represent a new option with which to overcome PTX-resistance in OvCa. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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17 pages, 1206 KiB

Open AccessArticle

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

by Enrico Ragni, Carlotta Perucca Orfei, Antonietta Rosa Silini, Alessandra Colombini, Marco Viganò, Ornella Parolini and Laura de Girolamo

Pharmaceutics 2020, 12(4), 347; https://doi.org/10.3390/pharmaceutics12040347 - 11 Apr 2020

Cited by 12 | Viewed by 3028

Abstract

Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and ΔCt method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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17 pages, 1799 KiB

Open AccessArticle

Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination

by Terutsugu Koya, Ippei Date, Haruhiko Kawaguchi, Asuka Watanabe, Takuya Sakamoto, Misa Togi, Tomohisa Kato, Jr., Kenichi Yoshida, Shunsuke Kojima, Ryu Yanagisawa, Shigeo Koido, Haruo Sugiyama and Shigetaka Shimodaira

Pharmaceutics 2020, 12(4), 305; https://doi.org/10.3390/pharmaceutics12040305 - 28 Mar 2020

Cited by 8 | Viewed by 4212

Abstract

With recent advances in cancer vaccination therapy targeting tumor-associated antigens (TAAs), dendritic cells (DCs) are considered to play a central role as a cell-based drug delivery system in the bioactive immune environment. Ex vivo generation of monocyte-derived DCs has been conventionally applied in adherent manufacturing systems with separate loading of TAAs before clinical use. We developed DCs pre-pulsed with Wilms’ tumor (WT1) peptides in low-adhesion culture maturation (WT1-DCs). Quality tests (viability, phenotype, and functions) of WT1-DCs were performed for process validation, and findings were compared with those for conventional DCs (cDCs). In comparative analyses, WT1-DCs showed an increase in viability and recovery of the DC/monocyte ratio, displaying lower levels of IL-10 (an immune suppressive cytokine) and a similar antigen-presenting ability in an in vitro cytotoxic T lymphocytes (CTLs) assay with cytomegalovirus, despite lower levels of CD80 and PD-L2. A clinical study revealed that WT1-specific CTLs (WT1-CTLs) were detected upon using the WT1-DCs vaccine in patients with cancer. A DC vaccine containing TAAs produced under an optimized manufacturing protocol is a potentially promising cell-based drug delivery system to induce acquired immunity. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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Review

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31 pages, 1075 KiB

Open AccessReview

Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side

by Laura Garcia-Perez, Anita Ordas, Kirsten Canté-Barrett, Pauline Meij, Karin Pike-Overzet, Arjan Lankester and Frank J. T. Staal

Pharmaceutics 2020, 12(6), 549; https://doi.org/10.3390/pharmaceutics12060549 - 13 Jun 2020

Cited by 6 | Viewed by 3786

Abstract

Recent clinical trials using patient’s own corrected hematopoietic stem cells (HSCs), such as for primary immunodeficiencies (Adenosine deaminase (ADA) deficiency, X-linked Severe Combined Immunodeficiency (SCID), X-linked chronic granulomatous disease (CGD), Wiskott–Aldrich Syndrome (WAS)), have yielded promising results in the clinic; endorsing gene therapy to become standard therapy for a number of diseases. However, the journey to achieve such a successful therapy is not easy, and several challenges have to be overcome. In this review, we will address several different challenges in the development of gene therapy for immune deficiencies using our own experience with Recombinase-activating gene 1 (RAG1) SCID as an example. We will discuss product development (targeting of the therapeutic cells and choice of a suitable vector and delivery method), the proof-of-concept (in vitro and in vivo efficacy, toxicology, and safety), and the final release steps to the clinic (scaling up, good manufacturing practice (GMP) procedures/protocols and regulatory hurdles). Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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17 pages, 1709 KiB

Open AccessReview

Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: From Basic Science to Clinics

by Carl Randall Harrell, Nemanja Jovicic, Valentin Djonov and Vladislav Volarevic

Pharmaceutics 2020, 12(5), 474; https://doi.org/10.3390/pharmaceutics12050474 - 22 May 2020

Cited by 65 | Viewed by 5411

Abstract

Mesenchymal stem cells (MSC) are, due to their immunosuppressive and regenerative properties, used as new therapeutic agents in cell-based therapy of inflammatory and degenerative diseases. A large number of experimental and clinical studies revealed that most of MSC-mediated beneficial effects were attributed to the effects of MSC-sourced exosomes (MSC-Exos). MSC-Exos are nano-sized extracellular vesicles that contain MSC-derived bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs)), enzymes, cytokines, chemokines, and growth factors) that modulate phenotype, function and homing of immune cells, and regulate survival and proliferation of parenchymal cells. In this review article, we emphasized current knowledge about molecular and cellular mechanisms that were responsible for MSC-Exos-based beneficial effects in experimental models and clinical trials. Additionally, we elaborated on the challenges of conventional MSC-Exos administration and proposed the use of new bioengineering and cellular modification techniques which could enhance therapeutic effects of MSC-Exos in alleviation of inflammatory and degenerative diseases. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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23 pages, 2773 KiB

Open AccessReview

Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments

by Prakash Gangadaran and Byeong-Cheol Ahn

Pharmaceutics 2020, 12(5), 442; https://doi.org/10.3390/pharmaceutics12050442 - 11 May 2020

Cited by 75 | Viewed by 5717

Abstract

Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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21 pages, 1401 KiB

Open AccessReview

Vascular Drug Delivery Using Carrier Red Blood Cells: Focus on RBC Surface Loading and Pharmacokinetics

by Patrick M. Glassman, Carlos H. Villa, Anvay Ukidve, Zongmin Zhao, Paige Smith, Samir Mitragotri, Alan J. Russell, Jacob S. Brenner and Vladimir R. Muzykantov

Pharmaceutics 2020, 12(5), 440; https://doi.org/10.3390/pharmaceutics12050440 - 09 May 2020

Cited by 66 | Viewed by 7340

Abstract

Red blood cells (RBC) have great potential as drug delivery systems, capable of producing unprecedented changes in pharmacokinetics, pharmacodynamics, and immunogenicity. Despite this great potential and nearly 50 years of research, it is only recently that RBC-mediated drug delivery has begun to move out of the academic lab and into industrial drug development. RBC loading with drugs can be performed in several ways—either via encapsulation within the RBC or surface coupling, and either ex vivo or in vivo—depending on the intended application. In this review, we briefly summarize currently used technologies for RBC loading/coupling with an eye on how pharmacokinetics is impacted. Additionally, we provide a detailed description of key ADME (absorption, distribution, metabolism, elimination) changes that would be expected for RBC-associated drugs and address unique features of RBC pharmacokinetics. As thorough understanding of pharmacokinetics is critical in successful translation to the clinic, we expect that this review will provide a jumping off point for further investigations into this area. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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22 pages, 1602 KiB

Open AccessReview

Erythrocytes as Carriers of Therapeutic Enzymes

by Bridget E. Bax

Pharmaceutics 2020, 12(5), 435; https://doi.org/10.3390/pharmaceutics12050435 - 08 May 2020

Cited by 20 | Viewed by 3812

Abstract

Therapeutic enzymes are administered for the treatment of a wide variety of diseases. They exert their effects through binding with a high affinity and specificity to disease-causing substrates to catalyze their conversion to a non-noxious product, to induce an advantageous physiological change. However, the metabolic and clinical efficacies of parenterally or intramuscularly administered therapeutic enzymes are very often limited by short circulatory half-lives and hypersensitive and immunogenic reactions. Over the past five decades, the erythrocyte carrier has been extensively studied as a strategy for overcoming these limitations and increasing therapeutic efficacy. This review examines the rationale for the different therapeutic strategies that have been applied to erythrocyte-mediated enzyme therapy. These strategies include their application as circulating bioreactors, targeting the monocyte–macrophage system, the coupling of enzymes to the surface of the erythrocyte and the engineering of CD34⁺ hematopoietic precursor cells for the expression of therapeutic enzymes. An overview of the diverse biomedical applications for which they have been investigated is also provided, including the detoxification of exogenous chemicals, thrombolytic therapy, enzyme replacement therapy for metabolic diseases and antitumor therapy. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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32 pages, 3431 KiB

Open AccessReview

Adipocyte-Based Cell Therapy in Oncology: The Role of Cancer-Associated Adipocytes and Their Reinterpretation as Delivery Platforms

by Raluca Munteanu, Anca Onaciu, Cristian Moldovan, Alina-Andreea Zimta, Diana Gulei, Angelo V. Paradiso, Vladimir Lazar and Ioana Berindan-Neagoe

Pharmaceutics 2020, 12(5), 402; https://doi.org/10.3390/pharmaceutics12050402 - 28 Apr 2020

Cited by 22 | Viewed by 4582

Abstract

Cancer-associated adipocytes have functional roles in tumor development through secreted adipocyte-derived factors and exosomes and also through metabolic symbiosis, where the malignant cells take up the lactate, fatty acids and glutamine produced by the neighboring adipocytes. Recent research has demonstrated the value of adipocytes as cell-based delivery platforms for drugs (or prodrugs), nucleic acids or loaded nanoparticles for cancer therapy. This strategy takes advantage of the biocompatibility of the delivery system, its ability to locate the tumor site and also the predisposition of cancer cells to come in functional contact with the adipocytes from the tumor microenvironment for metabolic sustenance. Also, their exosomal content can be used in the context of cancer stem cell reprogramming or as a delivery vehicle for different cargos, like non-coding nucleic acids. Moreover, the process of adipocytes isolation, processing and charging is quite straightforward, with minimal economical expenses. The present review comprehensively presents the role of adipocytes in cancer (in the context of obese and non-obese individuals), the main methods for isolation and characterization and also the current therapeutic applications of these cells as delivery platforms in the oncology sector. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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44 pages, 1302 KiB

Open AccessReview

Erythrocytes as Carriers: From Drug Delivery to Biosensors

by Larisa Koleva, Elizaveta Bovt, Fazoil Ataullakhanov and Elena Sinauridze

Pharmaceutics 2020, 12(3), 276; https://doi.org/10.3390/pharmaceutics12030276 - 18 Mar 2020

Cited by 63 | Viewed by 12808

Abstract

Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug’s action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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15 pages, 629 KiB

Open AccessReview

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data

by Gils Roex, Tom Feys, Yves Beguin, Tessa Kerre, Xavier Poiré, Philippe Lewalle, Peter Vandenberghe, Dominique Bron and Sébastien Anguille

Pharmaceutics 2020, 12(2), 194; https://doi.org/10.3390/pharmaceutics12020194 - 24 Feb 2020

Cited by 42 | Viewed by 9884

Abstract

Chimeric antigen receptor (CAR)-T-cell therapy is an innovative form of adoptive cell therapy that has revolutionized the treatment of certain hematological malignancies, including B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL). The treatment is currently also being studied in other B-cell neoplasms, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). CD19 and B-cell maturation antigen (BCMA) have been the most popular target antigens for CAR-T-cell immunotherapy of these malignancies. This review will discuss the efficacy and toxicity data from the pivotal clinical studies of CD19- and BCMA-targeted CAR-T-cell therapies in relapsed/refractory B-cell malignancies (NHL, ALL, CLL) and MM, respectively. Full article

(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)

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