Immunotherapy with interleukin-2 (IL2) and lymphokine-activated natural killer cells: Improvement of clinical responses in metastatic renal cell carcinoma patients previously treated with IL2

Escudier, Bernard; Farace, F; Angevin, Eric; Charpentier, François; Nitenberg, Gérard; Triebel, Frédéric; Hercend, Thierry

doi:10.1016/0959-8049(94)90460-x

Cited by 46 publications

(35 citation statements)

References 16 publications

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“…The early reaction of immune cells against target cells is helpful in anti-cancer therapy or treatment for acute inflammation. Primary human NK cell-based immunotherapeutic strategies against human cancers are encouraging because they trigger powerful immune responses with fewer side effects [29,30]. Prospective clinical trials should focus on enhancing NK cell function through an exact mechanism that has been thoroughly investigated and validated rather than non-specific NK cell expansion.…”

Section: Discussionmentioning

confidence: 99%

ERDR1 enhances human NK cell cytotoxicity through an actin-regulated degranulation-dependent pathway

Lee

Huh

Hur

et al. 2014

Cellular Immunology

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Section: Discussionmentioning

confidence: 99%

ERDR1 enhances human NK cell cytotoxicity through an actin-regulated degranulation-dependent pathway

Lee

Huh

Hur

et al. 2014

Cellular Immunology

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“…2,26,[39][40][41][42][43][44] Typically, these cultures are initiated using an enriched NK cell population isolated from apheresis products that have undergone CD3 ϩ T-cell depletion with or without CD56 ϩ selection to maximize NK cell purity. Utilization of feeder cells in NK cell cultures can dramatically enhance NK cell expansion numbers ex vivo, and this technique has been used recently for the large-scale expansion of clinical-grade NK cells.…”

Section: Ex Vivo Nk Cell Expansion Using Feeder Cellsmentioning

confidence: 99%

Bringing natural killer cells to the clinic: ex vivo manipulation

Childs

Berg

2013

Hematology

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Recently, there has been a substantial gain in our understanding of the role that natural killer (NK) cells play in mediating innate host immune responses against viruses and cancer. Although NK cells have long been known to be capable of killing cancer cells independently of antigen recognition, the full therapeutic potential of NK cell-based immunotherapy has yet to be realized. Here we review novel methods to activate and expand human NK cells ex vivo for adoptive transfer in humans, focusing on the important phenotypic and functional differences observed among freshly isolated, cytokine activated, and ex vivo-expanded NK populations. Natural killer cell therapy for cancer: a new hopeThe ability of natural killer (NK) cells to kill tumor cells without the need to recognize a tumor-specific antigen provides advantages over T cells and makes them appealing for investigation as effectors for immunotherapy. 1,2 There has recently been a substantial gain in our understanding of the role that NK cells play in mediating innate host immune responses against viruses and cancer. Although NK cells have long been known to be capable of killing cancer cells independently of antigen recognition, the full therapeutic potential of NK cell-based immunotherapy has yet to be realized. Here we review novel methods to activate and expand human NK cells ex vivo for adoptive transfer in humans, focusing on the important phenotypic and functional differences observed among freshly isolated, cytokine activated, and ex vivo-expanded NK populations. Ex vivo NK cell activation and expansionUnlike T cells, NK cells represent only a minor fraction of human lymphocytes. NK cells are defined by their CD3 Ϫ /CD56 ϩ phenotype, comprising 5% to 15% of circulating lymphocytes, and are commonly divided into CD56 dim CD16 ϩ (90%) and CD56 bright CD16 Ϫ (10%) subpopulations with distinct effector functions. Recently, investigators have shown that NK cell tumor cytotoxicity can be enhanced by disrupting NK cell signaling through inhibitory receptors such as KIR, PD-1, and NKG2A. 3,4 Furthermore, exposing tumors to drugs that down-regulate ligands for NK cell inhibitory receptors or up-regulate death receptors for NK cell effector molecules or ligands that bind NK cell-activating receptors can be used as a strategy to sensitize tumors to NK cell-mediated apoptosis. Recently, anti-PD-1 and anti-PD-L1 monoclonal antibodies and the immunomodulatory drug lenalidomide were shown to enhance both NK cell tumor trafficking and NK cell-mediated antibody-dependent cell-mediated cytotoxicity, and cytokine release against tumors while simultaneously suppressing regulatory T cell function. [5][6][7][8] Similarly, anti-CTLA-4 monoclonal antibodies have been shown to augment NK cell antibody-dependent cellmediated cytotoxicity and TNF␣ release against melanoma cells by Fc␥RIII (CD16) binding to antibody-bound tumor cells, as well as through regulatory T cell inactivation. 9-11 These data suggest these agents could be used in conjunction with autologous NK cell inf...

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“…Ten metastatic RCC patients received a combination of high-dose IL-2 and lymphokine-activated natural killer (LANAK) cell infusions. Partially effective clinical outcomes were observed with four complete responses and two additional patients whose tumor mass was further reduced [95]. Ishikawa et al [96] injected autologous NK cells together with IFN- into 9 patients with recurrent malignant glioma and showed that NK cell therapy was safe and partially effective.…”

Section: Adoptive Transfer Of Autologous Nk Cellsmentioning

confidence: 99%

NK cell-based cancer immunotherapy: from basic biology to clinical application

Yin

et al. 2015

Sci. China Life Sci.

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Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy. NK cell, cancer, cytokine infusion, adoptive transfer, immunotherapyCitation:

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Immunotherapy with interleukin-2 (IL2) and lymphokine-activated natural killer cells: Improvement of clinical responses in metastatic renal cell carcinoma patients previously treated with IL2

Cited by 46 publications

References 16 publications

ERDR1 enhances human NK cell cytotoxicity through an actin-regulated degranulation-dependent pathway

ERDR1 enhances human NK cell cytotoxicity through an actin-regulated degranulation-dependent pathway

Bringing natural killer cells to the clinic: ex vivo manipulation

NK cell-based cancer immunotherapy: from basic biology to clinical application

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