NK Cell-based Immunotherapies in Pediatric Oncology

McDowell, Kimberly A.; Hank, Jacquelyn A.; DeSantes, Kenneth; Capitini, Christian M.; Otto, Mario; Sondel, Paul M.

doi:10.1097/mph.0000000000000303

Cited by 16 publications

(13 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NK cells mediate innate immunity and have an important role in cancer immunosurveillance. NK cells are able to recognize tumor cells, due to their decreased HLA expression, and induce lysis before they grow into larger tumor aggregates (14,56,57). According to the current data, NK cells (CD3 -CD56 + CD16 + ) increased at the same time that Tregs decreased, at 2 weeks after CIK cell therapy.…”

Section: Discussionsupporting

confidence: 50%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P<0.05) concomitant with a significant decrease in Tregs (P<0.01) at 2 weeks post-infusion of CIK cells compared with the baseline. NK group 2D receptor (NKG2D) expression on NK cells was also significantly increased at 2 weeks post-infusion compared with the baseline (P<0.05). There was a positive correlation between NKG2D expression and the infusion number of CIK cells (P<0.05).

show abstract

Section: Discussionsupporting

confidence: 50%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Thus, combinations with other immunostimulatory agents may gain clinical interest with regard to the restoration of antitumor immunity. Besides cell therapy, few immunostimulatory agents are under clinical investigation (31). One of them is a plant-derived recombinant lectin I, aviscumine, that has demonstrated disease stabilizations in a number of solid tumors with tolerable toxicity for its immunostimulatory dose range in early clinical trials (17,19).…”

Section: Discussionmentioning

confidence: 99%

Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

et al. 2017

View full text Add to dashboard Cite

Abstract. Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers. Two effector-to-target cell ratios (12.5:1 and 25:1) were used by two independent investigators with a focus on the concentration-dependent effect (0.5 vs. 1 ng/ml aviscumine), reproducibility (first vs. second investigator) and the specificity of the effect by comparison to a heat-inactivated aliquot and interleukin 2 (IL-2) stimulation (10 ng/ml). The mediation of the effect via degranulation was demonstrated by flow cytometric analyses of CD107α expression. Statistics were performed with SPSS using Student's t-tests for normally distributed data. Aviscumine induced a significant and reproducible, concentration-dependent increase in NK cell cytotoxicity (n=22; P<0.01 for both concentrations and ratios), which was also demonstrated when administered in combination with IL-2 (n=12; 12.5:1 ratio, P<0.001; 25:1 ratio, P=0.025) and when compared with the heat-inactivated aliquots (n=12; 12.5:1, P= 0.004; 25:1 ratio, P= 0.007). The mediation of its effect via interferon γ degranulation was demonstrated by significantly enhanced CD107α expression (n=7; P=0.005). Taken together, the results indicate that aviscumine induced an increase in NK cell anticancer cytotoxicity. These results highlight its clinical potential as an immunostimulatory agent, particularly with regard to combined use with chemotherapeutics or immune checkpoint inhibitors. However, further studies are required.

show abstract

“…The immune system serves an important role in antitumor defenses via cytotoxic lymphocyte T cells and NK cells (23)(24)(25). NK cells possess a number of biological activities; NK cells not only directly recognize and lyse cancer cells, but also initiate anti-tumor immune responses by secreting a number of cytokines, including IFN-γ and TNF-α (26).…”

Section: Discussionmentioning

confidence: 99%

The anti‑hepatocellular carcinoma activity of Mel‑P15 is mediated by natural killer cells

Cui

Peng

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 µg/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61.15% following treatment with 2 mg/kg Mel-P15. In addition, the immune response was activated following Mel-P15 treatment. Mel-P15 treatment increased the spleen and thymus indices, promoted splenocyte proliferation, stimulated NK cytotoxicity and upregulated the secretion of cytokines, including interleukin-2, interferon-γ and tumor necrosis factor-α. In addition, the tumor inhibitory effect of Mel-P15 on BEL-7402-bearing nude mice was abrogated by the selective depletion of NK cells via the intraperitoneal injection of an anti-asialo GM-1 antibody. The results suggest that Mel-P15 inhibits tumor growth in vivo by promoting NK cell cytotoxicity. Mel-P15 may therefore be a potential immunotherapy candidate for the treatment of hepatocellular carcinoma.

show abstract

NK Cell-based Immunotherapies in Pediatric Oncology

Cited by 16 publications

References 138 publications

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

The anti‑hepatocellular carcinoma activity of Mel‑P15 is mediated by natural killer cells

Contact Info

Product

Resources

About