Adoptive NK cell therapy: a potential revolutionary approach in longevity therapeutics.

The aging process intricately involves immune system dynamics, with a crucial role in managing senescent cells (SNCs) and their senescence-associated secretory phenotypes (SASPs). Unfortunately, immunosenescence, a progressively dysregulated immunity with age, hampers effective SNC elimination, leading to accumulation, coupled with the release of SASPs, which, in turn, inhibits immunity and heightened susceptibility to aging-associated diseases (AADs). Natural killer (NK) cells, integral to the innate immune system, play a pivotal role in addressing SNCs swiftly.

Deregulated JNK signaling enhances apoptosis during hyperthermia.

Purpose: c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown.

Killer cell immunoglobulin-like receptor three domains long cytoplasmic tail 1 gene *007 may modulate disease progression of human immunodeficiency virus-1 infection in the Japanese population.

One of the KIR allele, KIR3DL1*007, was associated with the progression to acquired immunodeficiency syndrome and not with the susceptibility to HIV-1 infection in the Japanese and Indian populations, implying that KIR3DL1*007-positive NK cells might eliminate HIV-infected cells less effectively than NK cells bearing the other KIR3DL1 alleles or KIR3DS1 alleles.

Harnessing NK Cells to Control Metastasis.

In recent years, tumor immunotherapy has produced remarkable results in tumor treatment. Nevertheless, its effects are severely limited in patients with low or absent pre-existing T cell immunity. Accordingly, metastasis remains the major cause of tumor-associated death.

Exploring the Utility of NK Cells in COVID-19.

Coronavirus disease 2019 (COVID-19) can manifest as acute respiratory distress syndrome and is associated with substantial morbidity and mortality. Extensive data now indicate that immune responses to SARS-CoV-2 infection determine the COVID-19 disease course. A wide range of immunomodulatory agents have been tested for the treatment of COVID-19.

Synergistic Anti-tumor Effect of Dichloroacetate and Ivermectin.

We formerly reported that the combination of dichloroacetate, omeprazole, and tamoxifen blocked cancer progression by reducing lactic acid production and inducing superoxide production. Recently, ivermectin, a well-known anti-parasite drug, was reported to share the same mechanisms with them and have anti-tumor activity. Here, we present three patients in whom the combination of dichloroacetate, omeprazole (plus tamoxifen), and ivermectin dramatically relieved the symptoms accompanying cancer and sarcoma progression.

Extracellular vesicles from mesenchymal stem cells of dental pulp and adipose tissue display distinct transcriptomic characteristics suggestive of potential therapeutic targets.

Mesenchymal stem cells (MSCs) are isolated from various human tissues and used for therapy, in which beneficial effects are attributed mainly to mesenchymal stem cell-derived extracellular vesicles (MSC-EVs). Whereas MSCs of diverse tissue types share cardinal stem cell features, it is becoming evident that MSCs of each tissue type possess unique properties as well. For designing efficient stem cellbased therapies, it is crucial to understand the unique properties associated with MSCs and MSC-EVs of each tissue type.

Decrease in MAP3Ks expression enhances the cell death caused by hyperthermia.

Purpose: Hyperthermia is a promising anticancer treatment modality. However, the molecular mechanism underlying the thermal sensitivity of tumor cells is largely unknown. The aim of this study was to clarify how biochemical changes triggered by heat stimulate antitumor activity.

Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging.

Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections.

Variation in the manufacturing reproducibility of autologous cell-based products depending on raw material shipment conditions.

To prepare an autologous cell-based product in a cell processing facility, the raw material, which is collected from a patient, must first be shipped from a medical institution to the facility. The quality of this raw material varies depending on the patient, and variations due to transport methods also occur. Because the quality must be uniform and manufacturing processes need to be adjusted to account for these variations, determining the effect of shipment conditions on raw materials is very important for estimating cell manufacturability in the process design.

Comparative transcriptomic analysis of human mesenchymal stem cells derived from dental pulp and adipose tissues.

Mesenchymal stem cells (MSCs) have been isolated from various human tissues. Although they share cardinal stem cell features of self-renewal and multi-potency, they also seem to possess distinct characteristics depending on the tissue types they originated from. When developing stem cell-based therapies, MSCs with the most desirable characteristics should be chosen.

Cell-based immunotherapy in stage IIIA inflammatory breast cancer with declining innate immunity following successive chemotherapies: A case report.

Cancer stem cells in breast cancer migrating to the bone marrow may cause future metastasis, particularly during periods of decreased immunity. Natural killer (NK) cells have a role in immune surveillance and are able to target cancer stem cells. The present study reported a case in which NK cell-based autologous immune enhancement therapy was used combined with conventional treatments in a patient with stage IIIA breast cancer, yielding >28 months of disease-free survival.

Natural killer cells as a promising tool to tackle cancer-A review of sources, methodologies, and potentials.

Immune cell-based therapies are emerging as a promising tool to tackle malignancies, both solid tumors and selected hematological tumors. Vast experiences in literature have documented their safety and added survival benefits when such cell-based therapies are combined with the existing treatment options. Numerous methodologies of processing and in vitro expansion protocols of immune cells, such as the dendritic cells, natural killer (NK) cells, NKT cells, αβ T cells, so-called activated T lymphocytes, γδ T cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells, have been reported for use in cell-based therapies.

Experience of contamination during autologous cell manufacturing in cell processing facility under the Japanese Medical Practitioners Act and the Medical Care Act.

Cell therapy and regenerative medicine technologies require strict cell manufacturing procedures to be defined and addressed. Maintenance of the aseptic environment is critical to preclude extrinsic contamination risks, similar to conventional pharmaceutical manufacturing. However, intrinsic contamination risks exist in all cell manufacturing processes owing to the use of cells as the raw materials that cannot be sterilized, thus giving rise to the primary and secondary risks of cell contamination and cross-contamination, respectively.

APOBEC3H polymorphisms associated with the susceptibility to HIV-1 infection and AIDS progression in Japanese.

Human APOBEC3H (A3H) is a member of APOBEC3 cytidine deaminase family that potently restricts HIV-1 replication. Because A3H is genetically divergent with different intracellular stability and anti-HIV-1 activity in vitro, we investigated a possible association of A3H with susceptibility to HIV-1 infection and disease progression in Japanese populations. A total of 191 HIV-1-infected individuals (HIV group), 93 long-term non-progressors to AIDS (LTNP group) and 421 healthy controls were genotyped for two functional APOBEC3H polymorphisms, rs139292 and rs139297.

Combining autologous peripheral blood mononuclear cells with fibroblast growth factor therapy along with stringent infection control leading to successful limb salvage in diabetic patient with chronic renal failure and severe toe gangrene.

Peripheral arterial disease (PAD) is a common complication of Diabetes Mellitus (DM) and often culminates in amputation of the affected foot. Pseudomonas aeruginosa infections associated with PAD are difficult to treat due to their multi-drug resistance. Herein we report a 38 year old male who reported with DM, chronic kidney disease (CKD) and rest pain of the right second toe in October 2011.

Effective induction of melanoma-antigen-specific CD8+ T cells via Vγ9γδT cell expansion by CD56(high+) Interferon-α-induced dendritic cells.

Dendritic cells (DCs) can be differentiated from CD14+ monocytes in the presence of interferon-α (IFNα) and granulocyte/macrophage-colony stimulating factor (GM-CSF) in vitro and are known as IFN-DCs. Circulating blood CD56+ cells expressing high levels of CD14, HLA-DR and CD86 have been shown to spontaneously differentiate into DC-like cells in vitro after their isolation from blood. We show here that IFN-DCs expressing high levels of CD56 (hereafter, CD56(high+) IFN-DCs) can be differentiated in vitro from monocytes obtained as adherent cells from healthy donors and patients with metastatic melanoma.

Autologous immune enhancement therapy in Philadelphia chromosome positive acute lymphoblastic leukemia.

Advances in current treatment regimens in childhood acute lymphoblastic leukemia (ALL) have resulted in cure rates of 75-80 %. Some molecular genetic abnormalities confer a poor prognosis. Of these, the chromosomal translocation t (9;22)-Philadelphia chromosome is associated with the worst outcome in childhood ALL.

Autologous immune enhancement therapy in a case of gall bladder cancer stage IV after surgical resection and chemotherapy yielding a stable non-progressive disease.

Advanced gall bladder cancer generally has a poor prognosis and also shows decreased response to conventional therapies like chemotherapy and radiotherapy. Though surgical resection is the most common approach followed, the 1-year survival rate is only 10%. Herein, we report the outcome of administration of autologous natural killer cell and activated T lymphocyte-based autologous immune enhancement therapy (AIET) in a case of gall bladder cancer stage IV which was progressing in spite of surgical resection and several sittings of chemotherapy.

Ex vivo-expanded natural killer cells kill cancer cells more effectively than ex vivo-expanded γδ T cells or αβ T cells.

Adoptive immunotherapy of cancer is evolving with the development of novel technologies for generating a large number of activated killer cells such as natural killer (NK) cells, γδ T cells, and αβ T cells. We have recently established large-scale culture methods to generate activated NK cells from human peripheral blood, and demonstrated that expanded NK cells have higher cytotoxicity against cancer cells than freshly isolated NK cells. In this study, we compared cultured NK cells with cultured γδ T and αβ T cells that were prepared by conventional culture methods regarding the expression of cytotoxic molecules and cytotoxicity against cancer cells.

Efficacy of activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients.

Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced-toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the activation and expansion of NK and T cells was performed in Good Manufacturing Practice-certified clean rooms for ~12-15 days.

Age-old wisdom concerning cell-based therapies with added knowledge in the stem cell era: our perspectives.

Among the various strategies providing a cure for illness, cell-based therapies have caught the attention of the world with the advent of the "stem cell" era. Our inherent understanding indicates that stem cells have been in existence since the birth of multicellular organisms. However, the formal discovery of stem cells in the last century, followed by their intricate and extensive analysis, has led to clinical and translational efforts with the aim of using them in the treatment of conditions which don't have a definitive therapeutic strategy, has fueled our interest and expectations.

Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. The aim of our study was to observe the efficiency and safety of the combined treatment of radiofrequency ablation (RFA) with cellular immunotherapy (CIT) for HCC patients. In our study, 62 patients with HCC who were treated with radical RFA were divided into two groups: RFA alone (32 patients) and RFA/CIT (30 patients).

Autologous immune enhancement therapy: A case report of a stage IV colonic cancer.

Current modalities of cancer treatment, including surgery, chemotherapy and radiotherapy, show marginal therapeutic responses in cancer patients. In adoptive immunotherapy, interleukin-2 (IL-2) activated immune cells demonstrated notable results in patients with advanced malignant disease. The present study reports the efficacy and safety of repetitive infusions of autologous immune enhancement therapy (AIET) in a stage IV colonic cancer patient who had already received first-line chemotherapeutic drugs.

Autologous immune enhancement therapy against an advanced epithelioid sarcoma: A case report.

Rare types of cancer are often not effectively treated by approaches such as chemotherapy and radio-therapy, although their side-effects persist. Immunotherapy has been gaining attention worldwide with growing examples of its anticancer activity demonstrated . This case report describes a 35-year-old male who suffered from advanced epithelioid sarcoma and underwent 18 cycles of chemotherapy without any significant response, who suffered adverse effects that caused lung collapse.