New Advances in Cellular Immunotherapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (29 April 2024) | Viewed by 2847

Special Issue Editor


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Guest Editor
Department of Pediatrics, University Hospital La Paz, Universidad Autónoma de Madrid, Paseo de la Castellana 261, 28046 Madrid, Spain
Interests: adoptive therapy; hemato-oncology; hematopoietic stem cells and solid organ transplantation; graft versus host disease; genetic editing
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Special Issue Information

Dear Colleagues,

From the end of the nineteenth century to the modern day, immunology has produced new discoveries, showing us how powerful the immune cell response can be for treating severe diseases. Transplantation cell biology development is changing the field and improving transplantation outcomes, even overcoming classical axioms of immunology. The era of immunotherapy has focused not only on effector cells, such as T cells or natural killer (NK) cells, but also on antibody producers’ cells such as B lymphocytes, major antigen-presenting cells such as dendritic cells (DCs), and immune regulatory cell response such as mesenchymal stem cells (MSCs), hematopoietic progenitors, or myeloid-derived suppressor cells (MDSCs). Clinical studies with adoptive cell therapies and basic cell research continuously stimulate each other in a bidirectional manner. Since its initial implementation in cancer therapy, chimeric antigen receptor (CAR) expressed on immune cells has shown incredible regression rates in uncurable hematological malignancies. Unfortunately, until now, solid tumor cells and tumor cell microenvironments remain great challenges. In this Special Issue of Cells, I am glad to invite authors to submit original research articles, reviews, and prospective articles discussing recent advances in cellular immunotherapy in infants, pediatric, adolescents, young adults, and adults, proposing new strategies to overcome the current challenges in these promising therapies.

Dr. Antonio Pérez Martínez
Guest Editor

Manuscript Submission Information

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Keywords

  • adoptive cell therapy
  • immunotherapy
  • transplantation
  • immune evasions
  • tumor microenvironment
  • genetic editing
  • CAR T
  • TRUCK
  • NK

Published Papers (2 papers)

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Research

13 pages, 2521 KiB  
Article
Modulating Cholesterol Metabolism via ACAT1 Knockdown Enhances Anti-B-Cell Lymphoma Activities of CD19-Specific Chimeric Antigen Receptor T Cells by Improving the Cell Activation and Proliferation
by Qiong Su, Jie Yao, Muhammad Asad Farooq, Iqra Ajmal, Yixin Duan, Cong He, Xuefei Hu and Wenzheng Jiang
Cells 2024, 13(6), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/cells13060555 - 21 Mar 2024
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Abstract
CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is [...] Read more.
CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo. Full article
(This article belongs to the Special Issue New Advances in Cellular Immunotherapy)
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19 pages, 2702 KiB  
Article
The Development and Characterization of a Next-Generation Oncolytic Virus Armed with an Anti-PD-1 sdAb for Osteosarcoma Treatment In Vitro
by Theresa A. Higgins, Daniel J. Patton, Isabella M. Shimko-Lofano, Timothy L. Eller, Roberto Molinari, Maninder Sandey, Aliaa Ismail, Bruce F. Smith and Payal Agarwal
Cells 2024, 13(4), 351; https://0-doi-org.brum.beds.ac.uk/10.3390/cells13040351 - 17 Feb 2024
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Abstract
Osteosarcoma (OS) is a primary bone malignancy characterized by an aggressive nature, limited treatment options, low survival rate, and poor patient prognosis. Conditionally replicative adenoviruses (CRAds) armed with immune checkpoint inhibitors hold great potential for enhanced therapeutic efficacy. The present study aims to [...] Read more.
Osteosarcoma (OS) is a primary bone malignancy characterized by an aggressive nature, limited treatment options, low survival rate, and poor patient prognosis. Conditionally replicative adenoviruses (CRAds) armed with immune checkpoint inhibitors hold great potential for enhanced therapeutic efficacy. The present study aims to investigate the anti-tumor efficacy of CAV2-AU-M2, a CAV2-based CRAd armed with an anti-PD-1 single-domain antibody (sdAb), against OS cell lines in vitro. The infection, conditional replication, cytopathic effects, and cytotoxicity of CAV2-AU-M2 were tested in four different OS cell lines in two-dimensional (2D) and three-dimensional (3D) cell cultures. CAV2-AU-M2 showed selective replication in the OS cells and induced efficient tumor cell lysis and death. Moreover, CAV2-AU-M2 produced an anti-PD-1 sdAb that demonstrated effective binding to the PD-1 receptors. This study demonstrated the first CRAd armed with an anti-PD-1 sdAb. This combined approach of two distinct immunotherapies is intended to enhance the anti-tumor immune response in the tumor microenvironment. Full article
(This article belongs to the Special Issue New Advances in Cellular Immunotherapy)
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