A Novel Approach Inducing Transplant Tolerance By Activated Invariant Natural Killer T Cells With Co-Stimulatory Blockade.

Hirai, Toshihito; Ishii, Yasuyuki; Ikemiyagi, Masako; Fukuda, Elaine Y.; Omoto, Kazuya; Tanabe, Kazunari

doi:10.1097/00007890-201407151-00087

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…For the GVHD suppressive function of iNKT cells, their interplay with other immune regulatory cell populations is crucial. Multiple studies have provided compelling evidence that iNKT-induced interleukin-4 (IL4) dependent regulatory T (Treg) cell expansion drives inhibition of GVHD response in HCT (3,30,150,(198)(199)(200)(201). Treg cells have potent immune suppressive function in allogeneic HCT with demonstrated capability to suppress GVHD while preserving the GVT effect (202)(203)(204).…”

Section: Inkt Cell Therapy To Prevent and Treat Gvhdmentioning

confidence: 99%

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies

Boonchalermvichian,

Yan,

Gupta

et al. 2024

Front. Transplant.

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Invariant Natural Killer T cell therapy is an emerging platform of immunotherapy for cancer treatment. This unique cell population is a promising candidate for cell therapy for cancer treatment because of its inherent cytotoxicity against CD1d positive cancers as well as its ability to induce host CD8 T cell cross priming. Substantial evidence supports that iNKT cells can modulate myelomonocytic populations in the tumor microenvironment to ameliorate immune dysregulation to antagonize tumor progression. iNKT cells can also protect from graft-versus-host disease (GVHD) through several mechanisms, including the expansion of regulatory T cells (Treg). Ultimately, iNKT cell-based therapy can retain antitumor activity while providing protection against GVHD simultaneously. Therefore, these biological properties render iNKT cells as a promising “off-the-shelf” therapy for diverse hematological malignancies and possible solid tumors. Further the introduction of a chimeric antigen recetor (CAR) can further target iNKT cells and enhance function. We foresee that improved vector design and other strategies such as combinatorial treatments with small molecules or immune checkpoint inhibitors could improve CAR iNKT in vivo persistence, functionality and leverage anti-tumor activity along with the abatement of iNKT cell dysfunction or exhaustion.

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Section: Inkt Cell Therapy To Prevent and Treat Gvhdmentioning

confidence: 99%

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies

Boonchalermvichian,

Yan,

Gupta

et al. 2024

Front. Transplant.

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“…Abstracts #1416 and #2950 show that NKT cells activate MDSC to induce tolerance or prevent allograft rejection. Abstract #1415 describes a novel approach to induce suppressive NKT cells with the liposomal formulation of α‐galactosylceramide plus co‐stimulatory blockade. Abstract #2221 shows that RORγt + IL‐22‐producing NK cells ameliorate hepatic IRI.…”

Section: Nk/nkt Cellsmentioning

confidence: 99%

What’s Hot, What’s New at WTC—Basic Science

Bromberg

2015

American Journal of Transplantation

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The World Transplant Congress of 2014 presented a broad swath of science that touched on many disparate aspects of cell and organ transplantation, molecular and cellular immunology, systems biology, development, technology and translation into humans. A number of themes emerged this year. B cell biology and antibody chemistry were prominent, as they have been for several years. T cells, co-stimulatory blockade and regulatory T cells continue to dominate many aspects of immune research. Many new aspects of monocyte, macrophage, NK cell and NK T cell development, biology and regulation are now being explored. Diverse aspects of organ injury and the acute and chronic responses to injury are being investigated with new techniques, new targets and a resurgent vigor. Novel advances in xenotransplantation and experimental tolerance garnered much attention. Newer investigations in microbiota and nanotechnology promise significant gains in the near future. Lastly the 'omics of DNA, RNA, proteins, metabolites, bacteria and enzyme actions promise new understanding in biological systems and how to control those systems.Abbreviations: AMR, antibody mediated rejection; Breg, regulatory B cell; CyTOF, flow cytometry timeof-flow mass spectroscopy; DC, dendritic cell; HSC, hematopoietic stem cell; iPS, induced pluripotent stem cell; IRI, ischemia reperfusion injury; MDSC, myeloid derived suppressor cell; MSC, mesenchymal stem cell; TLR, Toll-like receptor B CellsB cells have been an obvious focus of transplant immunology for several decades, being the source of alloantibody and a major effector mechanism during acute and chronic graft rejection. However, over recent years, it has become evident that B cells simultaneously perform many other regulatory activities that are pro-or antiinflammatory or immunogenic. A number of reports demonstrate so-called B regulatory cells (Breg) that serve to dampen the immune response. Abstracts #657 (1), #658 (2), #2141 (3), and #2945 (4) demonstrate diverse roles for Breg in T cell effector memory responses, induction of Treg via TGFb, induction and maintenance viaTIM-1 signaling and promoting engraftment of hematopoietic stem cells, respectively. The implications of these reports are that indiscriminate depletion of B cells, such as with anti-CD20 mAbs, may actually be detrimental for graft survival by disrupting important regulatory pathways. These reports also identify potential targets for enhancing Breg presence, numbers and/or function; however, the diversity of Breg phenotypes currently precludes the ability to definitively identify this subset.Conversely, there are B helper subsets that promote inflammation and immunity and are distinguished by the expression of TIM-4 (Abstract #1413 (5)). This report identifies a potential target for depleting or inhibiting B helper function. Conversely, enhancing B helper function may improve immune responses to vaccines, cancer or microbial pathogens.Investigation of antibody function shows that some patients have immunoglobulins that recognize an u...

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A Novel Approach Inducing Transplant Tolerance By Activated Invariant Natural Killer T Cells With Co-Stimulatory Blockade.

Cited by 2 publications

References 37 publications

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies

What’s Hot, What’s New at WTC—Basic Science

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