Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Engineering enhanced chimeric antigen receptor-T cell therapy for solid tumors.

ABSTRACT: The early clinical success and subsequent US Food and Drug Administration approval of chimeric antigen receptor (CAR)-T cell therapy for leukemia and lymphoma affirm that engineered T cells can be a powerful treatment for hematologic malignancies. Yet this success has not been replicated in solid tumors. Numerous challenges emerged from clinical experience and well-controlled preclinical animal models must be met to enable safe and efficacious CAR-T cell therapy in solid tumors. Here, we review recent advances in bioengineering strategies developed to enhance CAR-T cell therapy in solid tumors, focusing on targeted single-gene perturbation, genetic circuits design, cytokine engineering, and interactive biomaterials. These bioengineering approaches present a unique set of tools that synergize with CAR-T cells to overcome obstacles in solid tumors and achieve robust and long-lasting therapeutic efficacy.

SUBMITTER: Neeser A

PROVIDER: S-EPMC10362352 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Engineering enhanced chimeric antigen receptor-T cell therapy for solid tumors.

Neeser A A Ramasubramanian R R Wang C C Ma L L

Immuno-oncology technology 20230524

The early clinical success and subsequent US Food and Drug Administration approval of chimeric antigen receptor (CAR)-T cell therapy for leukemia and lymphoma affirm that engineered T cells can be a powerful treatment for hematologic malignancies. Yet this success has not been replicated in solid tumors. Numerous challenges emerged from clinical experience and well-controlled preclinical animal models must be met to enable safe and efficacious CAR-T cell therapy in solid tumors. Here, we review ...[more]

PMID: 37483659

Similar Datasets

Chimeric antigen receptor T-cell therapy for solid tumors.

Project description:Chimeric antigen receptor (CAR) T cells are engineered constructs composed of synthetic receptors that direct T cells to surface antigens for subsequent elimination. Many CAR constructs are also manufactured with elements that augment T-cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematological malignancies (e.g., CD19 CARs in leukemias). This success is not yet extrapolated to solid tumors, and the reasons for this are being actively investigated. Here in this mini-review, we discuss some of the key hurdles encountered by CAR T cells in the solid tumor microenvironment.

| S-EPMC4849432 | biostudies-literature

Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors.

Project description:While impressive clinical responses have been observed using chimeric antigen receptor (CAR) T cells targeting CD19+ hematologic malignancies, limited clinical benefit has been observed using CAR T cells for a variety of solid tumors. Results of clinical studies have highlighted several obstacles which CAR T cells face in the context of solid tumors, including insufficient homing to tumor sites, lack of expansion and persistence, encountering a highly immunosuppressive tumor microenvironment, and heterogeneous antigen expression. In this review, we review clinical outcomes and discuss strategies to improve the antitumor activity of CAR T cells for solid tumors.

| S-EPMC6613829 | biostudies-literature

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors.

Project description:The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication.

| S-EPMC5767005 | biostudies-literature

Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy.

Project description:AbstractChildren and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing need for novel therapeutic strategies. Adoptive cellular therapy (ACT) has demonstrated activity in multiple adult cancer types, and opportunity exists to expand the use of this therapy in children. Employment of immunotherapy in the pediatric population has realized only modest overall clinical trial results, with success thus far restricted mainly to antibody-based therapies and chimeric antigen receptor T-cell therapies for lymphoid malignancy. As we improve our understanding of the orchestrated cellular and molecular mechanisms involved in ACT, this will provide biologic insight and improved ACT strategies for pediatric malignancies. This review focuses on ACT strategies outside of chimeric antigen receptor T-cell therapy, including completed and ongoing clinical trials, and highlights promising preclinical data in tumor-infiltrating lymphocytes that enhance the clinical efficacy of ACT for high-risk pediatric solid tumors.

| S-EPMC9847472 | biostudies-literature

Engineering chimeric antigen receptor T cells for solid tumour therapy.

Project description:Cell-based immunotherapy, for example, chimeric antigen receptor T (CAR-T) cell immunotherapy, has revolutionized cancer treatment, particularly for blood cancers. However, factors such as insufficient T cell tracking, tumour heterogeneity, inhibitory tumour microenvironment (TME) and T cell exhaustion limit the broad application of CAR-based immunotherapy for solid tumours. In particular, the TME is a complex and evolving entity, which is composed of cells of different types (e.g., cancer cells, immune cells and stromal cells), vasculature, soluble factors and extracellular matrix (ECM), with each component playing a critical role in CAR-T immunotherapy. Thus, developing approaches to mitigate the inhibitory TME factors is critical for future success in applying CAR-T cells for solid tumour treatment. Accordingly, understanding the bilateral interaction of CAR-T cells with the TME is in pressing need to pave the way for more efficient therapeutics. In the following review, we will discuss TME-associated aspects with an emphasis on T cell trafficking, ECM barriers, abnormal vasculature, solid tumour heterogenicity and immune suppressive microenvironment. We will then summarize current engineering strategies to overcome the challenges posed by the TME-associated factors. Lastly, the future directions for engineering efficient CAR-T cells for solid tumour therapy will be discussed.

| S-EPMC9736813 | biostudies-literature

Challenges and interventions of chimeric antigen receptor-T cell therapy in solid tumors.

Project description:Adoptive cellular therapy is rapidly improving immunotherapy in hematologic malignancies and several solid tumors. Remarkable clinical success has been achieved in chimeric antigen receptor (CAR)-T cell therapy which represents a paradigm-shifting strategy for the treatment of hematological malignancies. However, many challenges such as resistance, antigen heterogeneity, poor immune cell infiltration, immunosuppressive microenvironment, metabolic obstructive microenvironment, and T cell exhaustion remain as barriers to broader application especially in solid tumors. Encouragingly, the development of new approaches such as multidimensional omics and biomaterials technologies was aided to overcome these barriers. Here, in this perspective, we focus on the most recent clinical advancements, challenges, and strategies of immune cellular therapy in solid tumor treatment represented by CAR-T cell therapy, to provide new ideas to further overcome the bottleneck of immune cell therapy and anticipate future clinical advances.

| S-EPMC10334497 | biostudies-literature

Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities.

Project description:Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response. In this review, we will discuss the current stats and challenges of CAR-T cell therapy for solid tumors, and propose possibl e solutions and future perspectives.

| S-EPMC5685771 | biostudies-literature

Chimeric antigen receptor T cells: a novel therapy for solid tumors.

Project description:The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

| S-EPMC5372296 | biostudies-literature

Enhancing Chimeric Antigen Receptor T-Cell Efficacy in Solid Tumors.

Project description:Chimeric antigen receptor (CAR) T-cell therapy has been acclaimed as a revolution in cancer treatment following the impressive results in hematologic malignancies. Unfortunately, in patients with solid tumors, objectives responses to CAR T cells are still anecdotal, and important issues are driven by on-target but off-tumor activity of CAR T cells and by the extremely complex biology of solid tumors. Here, we will review the recent attempts to challenge the therapeutic impediments to CAR T-cell therapy in solid tumors. We will focus on the most promising strategies of antigen targeting to improve tumor specificity and address the tumor heterogeneity, efforts to circumvent the physical barriers of the tumor architecture such as subverted tumor vasculature, impediments of CAR T-cell trafficking and immune suppressive microenvironment.

| S-EPMC7269829 | biostudies-literature

Critical factors in chimeric antigen receptor-modified T-cell (CAR-T) therapy for solid tumors.

Project description:The success of chimeric antigen receptor-modified T-cell (CAR-T) therapy for B-cell lymphocyte malignancies targeting CD19 places it in a rapidly growing field in cancer immunotherapy for both hematological and solid tumors. However, the two types of tumor are quite different in the following respects. Solid tumors are characterized by complex vasculatures and matrix barriers that significantly affect T-cell functions and migration. Moreover, various immunosuppressive molecules expressed in the tumor microenvironment can impede T-cell activation, and the high metabolic rate of tumors competitively suppresses the metabolism of immune cells. All these factors will exert their influences on the development of a cancer, which is a dynamic balance between the host's immune system and the tumor. At present, solid tumors are treated primarily by surgical resection combined with radiotherapy and chemotherapy, a treatment process that is painful and not always effective. With advantages over traditional treatments, the recently developed CAR-T immunotherapy has been applied and has shown highly promising results. Nevertheless, the complexity of solid tumors presents a great challenge to this technique. This review focuses on elucidating the factors influencing the anti-tumor effects of CAR-T in the specific tumor environment, and hence exploring feasible approaches to overcome them.

| S-EPMC6309774 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data