Adoptive immunotherapy with T cells, genetically modified to express a tumor-reactive chimeric antigen receptor (CAR), is an innovative and rapidly developing life-saving treatment for cancer patients without other therapeutic opportunities. CAR-T cell therapy has proven effective only in hematological malignancies. However, although by now only a few clinical trials had promising outcomes, we predict that CAR-T therapy will eventually become an established treatment for several solid tumors. Oncolytic viruses (OVs) can selectively replicate in and kill cancer cells without harming healthy cells. They can stimulate an immune response against the tumor, because OVs potentially stimulate adaptive immunity and innate components of the host immune system. Using CAR-T cells along with oncolytic viruses may enhance the efficacy of CAR-T cell therapy in destroying solid tumors by increasing the tumor penetrance of T cells and reducing the immune suppression by the tumor microenvironment. This review describes recent advances in the design of oncolytic viruses and CAR-T cells while providing an overview of the potential combination of oncolytic virotherapy with CAR-T cells for solid cancers. In this review, we will focus on the host-virus interaction in the tumor microenvironment to reverse local immunosuppression and to develop CAR-T cell effector function.
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http://dx.doi.org/10.3389/fimmu.2024.1455163 | DOI Listing |
J Hematol Oncol
January 2025
Bavarian Cancer Research Center (BZKF), R/R ALL Study Group, Bavaria, Germany.
Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.
View Article and Find Full Text PDFNat Protoc
January 2025
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
The clinical potential of current chimeric antigen receptor-engineered T (CAR-T) cell therapy is hampered by its autologous nature that poses considerable challenges in manufacturing, costs and patient selection. This spurs demand for off-the-shelf therapies. Here we introduce an ex vivo feeder-free culture method to differentiate gene-engineered hematopoietic stem and progenitor (HSP) cells into allogeneic invariant natural killer T (NKT) cells and their CAR-armed derivatives (CAR-NKT cells).
View Article and Find Full Text PDFBone Marrow Transplant
January 2025
Vanderbilt University Medical Center, Nashville, TN, USA.
Methods Cell Biol
January 2025
Division of Clinical Pharmacology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and LMU University Hospital, Munich, Germany; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany. Electronic address:
Treatment with autologous chimeric antigen receptor (CAR)-modified T cells can achieve outstanding clinical response rates in heavily pretreated patients with B and plasma cell malignancies. However, relapses occur, and they limit the efficacy of this promising treatment approach. The complex GMP-compliant production and high treatment costs cause that CAR T cells cannot yet be used in a broad population.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Biotherapy Center & Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
Background: Glucose deprivation inhibits T-cell metabolism and function. Glucose levels are low in the tumor microenvironment of solid tumors and insufficient glucose uptake limits the antitumor response of T cells. Furthermore, glucose restriction can contribute to the failure of chimeric antigen receptor T (CAR-T) cell therapy for solid tumors.
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