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Special Issue "Cell Therapy"

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 November 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Shin Mineishi

Bone Marrow Transplant Program, Penn State Hershey Medical Center, 500 University Drive, P.O Box 850, Hershey, PA 17033, USA
Website | E-Mail
Interests: bone marrow transplantation; graft versus host disease; complications after stem cell transplantation; reduced intensity stem cell transplantation; HLA-mismatch stem cell transplantation; graft engineering; cell therapy; and gene therapy

Special Issue Information

Dear Colleague,

The journal Pharmaceuticals will be publishing a Special Issue covering the topic “Cell Therapy” and I am cordially inviting you to contribute an article to this volume.  This is a timely issue as cell therapy has recently evolved from laboratory research/animal models into clinical trials showing promising results.

Cell therapy covers a wide variety of research, from proof of principle experiments to clinical cell transplant/cell therapy, including immune cell therapy, vaccine therapy, gene therapy, and others. Most of the area may belong to either cancer cell therapy or regenerative medicine. For this issue, I would like to invite manuscript submissions from authors engaged in a wide variety of projects in order to meet the needs of interested readers from various backgrounds.

I hope this issue facilitates discussions among investigators in the many different areas of cell therapy which may lead to further steps in the pertinent investigations.

Prof. Dr. Shin Mineishi
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access quarterly 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 800 CHF (Swiss Francs).

Keywords

  • cell therapy
  • cell transplant
  • immune cell therapy
  • vaccine therapy
  • gene therapy
  • cancer cell therapy
  • regenerative medicine

Published Papers (5 papers)

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Review

Open AccessReview Immunotherapeutic Applications of NK Cells
Pharmaceuticals 2015, 8(2), 250-256; doi:10.3390/ph8020250
Received: 26 January 2015 / Accepted: 13 May 2015 / Published: 25 May 2015
Cited by 3 | PDF Full-text (650 KB) | HTML Full-text | XML Full-text
Abstract
Natural Killer (NK) cells are lymphoid cells that exhibit an innate response against virus-infected cells. These cells are also capable of mounting an immune response against tumor cells after education through major histocompatibility complex (MHC) class I molecules. NK cell regulation is mediated
[...] Read more.
Natural Killer (NK) cells are lymphoid cells that exhibit an innate response against virus-infected cells. These cells are also capable of mounting an immune response against tumor cells after education through major histocompatibility complex (MHC) class I molecules. NK cell regulation is mediated through IFN-gamma and IL-15, important cytokines which can drive NK cell expansion in vivo. Previous studies have shown effective infusion of allogeneic NK cells after lymphodepleting regimens with induction of remission of poor prognosis acute myeloid leukemia (AML). Challenges remain in the expansion of these NK cells once infused and in their education to recognize tumor targets. A principal mechanism of tumor recognition is through KIR mismatch in cells lacking self MHC I molecules. Activating KIRs exist, though their ligands are unknown at this time. Impacting NK cell expansion and education in vivo has been challenging, and thus far clinical applications of NK cells have shown promise in helping to maintain remission in humans, though this remission has not been maintained. Future efforts to utilize NK cells clinically are focusing on developing more consistency in successful expansion of NK cell and educating them to recognize their tumor targets. Additional efforts to utilize novel antibody-based therapy to engage NK cells to their tumor targets are also in development. Full article
(This article belongs to the Special Issue Cell Therapy)
Open AccessReview Seatbelts in CAR therapy: How Safe Are CARS?
Pharmaceuticals 2015, 8(2), 230-249; doi:10.3390/ph8020230
Received: 9 December 2014 / Revised: 29 April 2015 / Accepted: 4 May 2015 / Published: 8 May 2015
Cited by 8 | PDF Full-text (977 KB) | HTML Full-text | XML Full-text
Abstract
T-cells genetically redirected with a chimeric antigen receptor (CAR) to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to
[...] Read more.
T-cells genetically redirected with a chimeric antigen receptor (CAR) to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to prevent or abate serious adverse events are required. Pharmacologic therapies; suicide genes; or novel strategies to limit the cytotoxic effect only to malignant cells are under active investigations. In this review, we summarize results and toxicities of investigations employing CAR redirected T-cells, with a focus on published strategies to grant safety of this promising cellular application. Full article
(This article belongs to the Special Issue Cell Therapy)
Open AccessReview Wharton’s Jelly-Derived Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for the Management of Graft-versus-Host Disease
Pharmaceuticals 2015, 8(2), 196-220; doi:10.3390/ph8020196
Received: 10 December 2014 / Revised: 13 March 2015 / Accepted: 8 April 2015 / Published: 16 April 2015
Cited by 5 | PDF Full-text (758 KB) | HTML Full-text | XML Full-text
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and
[...] Read more.
Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton’s jelly (WJ)-derived mesenchymal stromal cells (MSCs) as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines) to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD. Full article
(This article belongs to the Special Issue Cell Therapy)
Open AccessReview γδ T Cell Immunotherapy—A Review
Pharmaceuticals 2015, 8(1), 40-61; doi:10.3390/ph8010040
Received: 6 January 2015 / Accepted: 2 February 2015 / Published: 12 February 2015
Cited by 5 | PDF Full-text (778 KB) | HTML Full-text | XML Full-text
Abstract
Cancer immunotherapy utilizing Vγ9Vδ2 T cells has been developed over the past decade. A large number of clinical trials have been conducted on various types of solid tumors as well as hematological malignancies. Vγ9Vδ2 T cell-based immunotherapy can be classified into two categories
[...] Read more.
Cancer immunotherapy utilizing Vγ9Vδ2 T cells has been developed over the past decade. A large number of clinical trials have been conducted on various types of solid tumors as well as hematological malignancies. Vγ9Vδ2 T cell-based immunotherapy can be classified into two categories based on the methods of activation and expansion of these cells. Although the in vivo expansion of Vγ9Vδ2 T cells by phosphoantigens or nitrogen-containing bisphosphonates (N-bis) has been translated to early-phase clinical trials, in which the safety of the treatment was confirmed, problems such as activation-induced Vγ9Vδ2 T cell anergy and a decrease in the number of peripheral blood Vγ9Vδ2 T cells after infusion of these stimulants have not yet been solved. In addition, it is difficult to ex vivo expand Vγ9Vδ2 T cells from advanced cancer patients with decreased initial numbers of peripheral blood Vγ9Vδ2 T cells. In this article, we review the clinical studies and reports targeting Vγ9Vδ2 T cells and discuss the development and improvement of Vγ9Vδ2 T cell-based cancer immunotherapy. Full article
(This article belongs to the Special Issue Cell Therapy)
Open AccessReview Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors
Pharmaceuticals 2014, 7(12), 1049-1068; doi:10.3390/ph7121049
Received: 3 November 2014 / Revised: 26 November 2014 / Accepted: 8 December 2014 / Published: 15 December 2014
Cited by 3 | PDF Full-text (742 KB) | HTML Full-text | XML Full-text
Abstract
Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma.
[...] Read more.
Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as “cellular drugs”. As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs), transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR) gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy. Full article
(This article belongs to the Special Issue Cell Therapy)

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