The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

Nelson, Adam; Lukacs, Jordan D; Johnston, Brent

doi:10.3390/cancers13205174

Cited by 68 publications

(47 citation statements)

References 229 publications

(377 reference statements)

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“…One of the barriers our proposed platform addresses is the difficulty of recruiting peripheral iNKT cells to the tumor site [ 36 ]. Tumor signaling induces the downregulation of iNKT cell IFN-γ secretion relative to immunosuppressive IL-4 cytokine, suppressing tumor infiltration to evade iNKT anti-tumor cytotoxicity [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Zhou

Wilson

et al. 2022

IJMS

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Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision.

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Section: Discussionmentioning

confidence: 99%

Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Zhou

Wilson

et al. 2022

IJMS

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“…Several studies have shown a relationship between the number and activity of iNKT cells and clinical outcomes, making these cells an interesting therapeutic tool against cancer development and metastasis ( 99 , 101 ).…”

Section: Overview Of Nsclc Tumor Immune Microenvironmentmentioning

confidence: 99%

Host-Related Factors as Targetable Drivers of Immunotherapy Response in Non-Small Cell Lung Cancer Patients

Baci

Cekani²,

Imperatori³

et al. 2022

Front. Immunol.

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Despite some significant therapeutic breakthroughs leading to immunotherapy, a high percentage of patients with non-small cell lung cancer (NSCLC) do not respond to treatment on relapse, thus experiencing poor prognosis and survival. The unsatisfying results could be related to the features of the tumor immune microenvironment and the dynamic interactions between a tumor and immune infiltrate. Host–tumor interactions strongly influence the course of disease and response to therapies. Thus, targeting host-associated factors by restoring their physiologic functions altered by the presence of a tumor represents a new therapeutic approach to control tumor development and progression. In NSCLC, the immunogenic tumor balance is shifted negatively toward immunosuppression due to the release of inhibitory factors as well as the presence of immunosuppressive cells. Among these cells, there are myeloid-derived suppressor cells, regulatory T cells that can generate a tumor-permissive milieu by reprogramming the cells of the hosts such as tumor-associated macrophages, tumor-associated neutrophils, natural killer cells, dendritic cells, and mast cells that acquire tumor-supporting phenotypes and functions. This review highlights the current knowledge of the involvement of host-related factors, including innate and adaptive immunity in orchestrating the tumor cell fate and the primary resistance mechanisms to immunotherapy in NSCLC. Finally, we discuss combinational therapeutic strategies targeting different aspects of the tumor immune microenvironment (TIME) to prime the host response. Further research dissecting the characteristics and dynamic interactions within the interface host–tumor is necessary to improve a patient fitness immune response and provide answers regarding the immunotherapy efficacy, with the aim to develop more successful treatments for NSCLC.

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“…In hematological setting, CAR-γδ T cells showed the ability to cross-present tumor antigens to αβ T cells in vitro, as well as antigen-dependent and independent cytotoxicity. More recently, the feasibility and antitumor activity of allogeneic Vδ1, the subset more frequent within TIL, was reported in a mouse model of hepatocellular carcinoma [ 66 ], and a similar approach is now undergoing clinical trial testing [ 65 ].…”

Section: The Cells To Engineermentioning

confidence: 99%

Chimeric Antigen Receptor Immunotherapy for Solid Tumors: Choosing the Right Ingredients for the Perfect Recipe

Castiello¹,

Santodonato²,

Napolitano³

et al. 2022

Cancers

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Chimeric antigen receptor T cell therapies are revolutionizing the clinical practice of hematological tumors, whereas minimal progresses have been achieved in the solid tumor arena. Multiple reasons have been ascribed to this slower pace: The higher heterogeneity, the hurdles of defining reliable tumor antigens to target, and the broad repertoire of immune escape strategies developed by solid tumors are considered among the major ones. Currently, several CAR therapies are being investigated in preclinical and early clinical trials against solid tumors differing in the type of construct, the cells that are engineered, and the additional signals included with the CAR constructs to overcome solid tumor barriers. Additionally, novel approaches in development aim at overcoming some of the limitations that emerged with the approved therapies, such as large-scale manufacturing, duration of manufacturing, and logistical issues. In this review, we analyze the advantages and challenges of the different approaches under development, balancing the scientific evidences supporting specific choices with the manufacturing and regulatory issues that are essential for their further clinical development.

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The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

Cited by 68 publications

References 229 publications

Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Host-Related Factors as Targetable Drivers of Immunotherapy Response in Non-Small Cell Lung Cancer Patients

Chimeric Antigen Receptor Immunotherapy for Solid Tumors: Choosing the Right Ingredients for the Perfect Recipe

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