Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease

Davies, James O. J.; Stringaris, Kate; Barrett, A. John; Rezvani, Katayoun

doi:10.1016/j.jcyt.2014.03.009

Cited by 53 publications

(46 citation statements)

References 134 publications

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“…Importantly, in both approaches, very few incidents of autoimmunity or graft-versushost reactivity were observed, arguing against missing self-attacks on normal host cells. Although some antitumor effects have been documented, the overall impression from these early trials is that there is much room for improvement (15,16).…”

Section: Introductionmentioning

confidence: 99%

Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response

Wagner

Wickström

Tallerico

et al. 2016

Cancer Immunology Research

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Natural killer (NK) cells are most efficient if their targets do not express self MHC class I, because NK cells carry inhibitory receptors that interfere with activating their cytotoxic pathway. Clinicians have taken advantage of this by adoptively transferring haploidentical NK cells into patients to mediate an effective graftversus-leukemia response. With a similar rationale, antibody blockade of MHC class I-specific inhibitory NK cell receptors is currently being tested in clinical trials. Both approaches are challenged by the emerging concept that NK cells may constantly adapt or "tune" their responsiveness according to the amount of self MHC class I that they sense on surrounding cells. Hence, these therapeutic attempts would initially result in increased killing of tumor cells, but a parallel adaptation process might ultimately lead to impaired antitumor efficacy. We have investigated this question in two mouse models: inhibitory receptor blockade in vivo and adoptive transfer to MHC class I-disparate hosts. We show that changed self-perception via inhibitory receptors in mature NK cells reprograms the reactivity such that tolerance to healthy cells is always preserved. However, reactivity against cancer cells lacking critical MHC class I molecules (missing self-reactivity) still remains or may even be increased. This dissociation between activity against healthy cells and tumor cells may provide an answer as to why NK cells mediate graftversus-leukemia effects without causing graft-versus-host disease and may also be utilized to improve immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response

Wagner

Wickström

Tallerico

et al. 2016

Cancer Immunology Research

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“…Innate lymphoid population (NK cells, NKT cell, gdT cells) are able to respond early to inflammation and may in this way be crucial in early recognition of malignant cell alterations (Woo et al 2015). Natural killer cells have fundamental antitumoral features: They kill cells with absent or reduced MHC class I molecule expression, which is often the case during tumor progression (Davies et al 2014). Infiltration of solid tumors with NK cells may lead to a more favourable prognosis (Pietra et al 2012).…”

Section: Innate Immune Mechanismsmentioning

confidence: 99%

Prospect for immunological therapies of the equine malignant melanoma

Cavalleri¹,

Mählmann²,

Schuberth³

et al. 2015

PHK

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Summary: Although equine melanocytic neoplasms occur frequently, at least in grey horses, their existence is neglected frequently, despite their potentially severe clinical consequences. Immune-based therapies have been investigated in human metastatic melanoma and offer encouraging results. Researchers have recently begun to explore the immunological approach in equine malignant melanoma (EMM) with some success. Therefore, this review aims at giving a short overview of the nature of EMM and providing insight into the immunological basis of melanocytic neoplasms in general. Equine malignant melanoma is a true neoplasm with a genetic basis. Initially they show a slow invasive growth, but they have the potential to metastasize. EMM and human malignant melanomas share various common histopathologic features. For the immune system eradication of the tumor is a challenge. Although solid tumors are often infiltrated with immune cells, they usually do not induce a significant tumor remission. The antitumoral immune response depends on factors of the innate immune system interacting in a coordinated fashion with the adaptive immune system. Antigen-presenting cells, neutrophilic granulocytes, and lymphoid cells may elicit antitumoral effects. This innate response precedes a downstream antigen-specific response. In the tumor microenvironment of solid tumors immune suppressive factors can induce immune escape mechanisms of the tumors. Immunological therapies of EMM include blockage of histamine 2 receptors on melanoma cells and lymphocytes, cancer vaccines and gene therapeutic approaches. This article focuses on the immunological therapeutic approach of EMM and gives an outlook on future implications.

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“…2 More recent evidence suggests that survival may be improved by haploidentical natural killer (NK) cell transplants, 3,4 and strategies that augment the efficacy of NK-cell destruction of leukemic targets would thus be of utmost clinical importance. 5 Herpes simplex virus-1 (HSV-1) is a large (.150 kb) doublestranded DNA oncolytic virus (OV) of the a-subfamily of Herpesviridae that has been engineered in various ways to preferentially infect and lyse transformed cells, leaving normal cells relatively unharmed. 6 Various OVs have shown excellent safety and promising therapeutic efficacy against solid tumors in a number of clinical trials, [7][8][9][10][11][12][13][14] and recently, Russell et al demonstrated that OV therapy may offer a therapeutic benefit for patients with hematologic malignancies.…”

Section: Introductionmentioning

confidence: 99%