Adoptive Cell Therapy in Pediatric and Young Adult Solid Tumors: Current Status and Future Directions

Ligon, John A.; Wessel, Kristin M.; Shah, Nirali N.; Glod, John

doi:10.3389/fimmu.2022.846346

Cited by 11 publications

(4 citation statements)

References 114 publications

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“…37,38 ACT engineering or combination therapy with other agents that help allow ACT to overcome these challenges will be necessary in the optimization of this therapy for solid tumors. 39 Although there are limitations to the success of TIL-based therapies, there are opportunities to optimize this process. The ability to expand TILs ex-vivo provides an opportunity to modify and optimize the infusion product with methods like enrichment of tumor-reactive TILs, genetic engineering, and modulation of T cell metabolism.…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating lymphocyte therapy: an overview

Vlashi¹,

Tawil²

2023

JABB

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Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating lymphocyte therapy: an overview

Vlashi¹,

Tawil²

2023

JABB

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“…The fourth-generation CAR-T cells, also known as T cells redirect for universal cytokine killings (TRUCKs) were designed to release cytokines into tumor tissues when the CARs bound to targeted antigens. The cytokine which was overexpressed in CAR was IL-12, a highly effective substance that used NK cells to destroy tumor cells that were not identified by CARs and boosted the IFN-γ, GZMB and perforin secretion of T cells [ 95 ]. An IL-2 receptor domain between the CD3 and CD28 signaling domains as well as a STAT3-binding motif were recently added to a unique CAR that followed the framework of the second generation [ 96 ].…”

Section: Types Of Adoptive Cell Therapymentioning

confidence: 99%

The potential and promise for clinical application of adoptive T cell therapy in cancer

Li,

Zheng,

Liu

et al. 2024

J Transl Med

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Adoptive cell therapy has revolutionized cancer treatment, especially for hematologic malignancies. T cells are the most extensively utilized cells in adoptive cell therapy. Currently, tumor-infiltrating lymphocytes, T cell receptor-transgenic T cells and chimeric antigen receptor T cells are the three main adoptive T cell therapies. Tumor-infiltrating lymphocytes kill tumors by reinfusing enlarged lymphocytes that naturally target tumor-specific antigens into the patient. T cell receptor-transgenic T cells have the ability to specifically destroy tumor cells via the precise recognition of exogenous T cell receptors with major histocompatibility complex. Chimeric antigen receptor T cells transfer genes with specific antigen recognition structural domains and T cell activation signals into T cells, allowing T cells to attack tumors without the assistance of major histocompatibility complex. Many barriers have been demonstrated to affect the clinical efficacy of adoptive T cell therapy, such as tumor heterogeneity and antigen loss, hard trafficking and infiltration, immunosuppressive tumor microenvironment and T cell exhaustion. Several strategies to improve the efficacy of adoptive T cell therapy have been explored, including multispecific chimeric antigen receptor T cell therapy, combination with immune checkpoint blockade, targeting the immunosuppressive tumor microenvironment, etc. In this review, we will summarize the current status and clinical application, followed by major bottlenecks in adoptive T cell therapy. In addition, we will discuss the promising strategies to improve adoptive T cell therapy. Adoptive T cell therapy will result in even more incredible advancements in solid tumors if the aforementioned problems can be handled. Graphical abstract

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“…Several ATMPs are under investigation in clinical trials against solid tumors, but only a few have involved pediatric patients [ 168 , 169 ]. Most of these therapies are based on the use of T cells, but NK cells and monocytes are gaining increasing attention [ 170 , 171 ].…”

Section: The Role Of Immunomodulating Agents On Tmementioning

confidence: 99%

Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy

Belgiovine,

Mebelli,

Raffaele

et al. 2024

IJMS

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Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.

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Adoptive Cell Therapy in Pediatric and Young Adult Solid Tumors: Current Status and Future Directions

Cited by 11 publications

References 114 publications

Tumor-infiltrating lymphocyte therapy: an overview

Tumor-infiltrating lymphocyte therapy: an overview

The potential and promise for clinical application of adoptive T cell therapy in cancer

Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy

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