Killer Therapy !FULL!
We devised an innovative type of immunocell therapy called BRM (biological response modifier)-activated killer (BAK) therapy, which utilizes most of non-MHC (major histocompatibility complex) restricted lymphocytes, CD56+ cells including gammadelta T cells and NK cells. Peripheral blood lymphocytes were selected by immobilizing them with anti-CD3 monoclonal antibody, cultured for 2 weeks with serum-free medium containing IL-2, and then were reactivated by 1,000 U/ml of IFN-alpha for 15 min. The patients were infused with about 6x10(9) BAK cells by intravenous drip infusion at 1-month intervals. All advanced solid cancer patients who had received chemotherapy but for whom it was not effective or have refused chemotherapy were included in the present study. A good marker of impairment of host immune response by chemotherapy is an immunosuppressive acidic protein (IAP) level in serum above 580 microg/ml; survival rates were compared with the high (> 580 microg/ml) and the low (
Directed by Barry Jay (Ashes), the movie explores the disturbing thoughts and ensuing therapy sessions of a young man named Brian. Thom Mathews leads the cast as family patriarch John Langston, and here's what the actor has to say about taking on a lead role once again in the horror genre.
In Killer Therapy, Brian is a disturbed child with sociopathic tendencies dealing with a father who doesn't love him, a mother unconvinced of his violent nature, and a newly adopted sister he believes is there to replace him. After a series of escalating violent incidents, he is bounced around from failed therapist to failed therapist, maturing into a young man still unable to escape his anger issues. When his life eventually falls apart by his own choices, Brian blames his series of failed therapists, embracing his dark nature and taking his revenge on everyone who ever wronged him - one by one, finally understanding that accepting who you are inside can be the best therapy.
It was previously believed that Thom Mathews would appear as a fictionalized version of himself in the Friday the 13th reunion movie 13 Fanboy. Directed by Friday the 13th: A New Beginning star Deborah Voorhees, the meta-slasher follows a masked killer taking out many beloved stars of the popular horror franchise. Apparently, Thom Mathews is no longer involved with the project. Some of the other names from the series confirmed to appear do include Corey Feldman, Kane Hodder, Lar Park Lincoln, CJ Graham, Jennifer Banko, Judie Aronson, and Adrienne King. The movie is now currently in production after running a successful crowdfunding campaign on Indiegogo.
After a series of escalating violent incidents, Brian is moved from failed therapist to failed therapist, maturing into a young man still unable to escape his anger issues.When his life eventually falls apart by his own choices, Brian blames his series of failed therapists, embracing his dark nature and taking his revenge on everyone who ever wronged him, one by one, finally understanding that accepting who you are inside can be the best therapy.
Bloody has the trailer for the movie, starring Return of the Living Dead alum Thom Mathews, who explores the disturbing thoughts and ensuing therapy sessions of a young man named Brian.
Mr. X had many of the traits associated with serial killers in the literature yet was dissimilar in many others. On the one hand, he shared the family background of many serial killers. He certainly shared the obsessive homicidal fantasies and plans that preclude serial murder. He had also obtained a weapon.
Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.
A CAR is composed of three domains: an ectodomain, the transmembrane region and a cytoplasmic activation tail [6, 10]. The ectodomain contains a single-chain variable fragment (scFv), usually derived from antibodies that provides the ability to specifically recognize tumor antigens expressed on cancerous cells . The transmembrane domain anchors the CAR structure on the effector cell membrane . Once the CAR recognizes and gets triggered by its specific antigen, the intracellular activation domain(s) of the CAR will signal, resulting in downstream processes that facilitate the killing of target cells [13, 14]. Numerous immune effector cells, like T cells, γδsT cells, natural killer (NK) cells, NKT cells, and macrophages, have been equipped with a CAR and were shown to be able to mediate anticancer responses in preclinical studies and clinical trials [4, 15, 16]. In 2017, the US Food and Drug Administration (FDA) approved the first two CAR-T treatments for CD19+ hematologic malignancies (axicabtagene ciloleucel and tisagenlecleucel) [1, 17].
An interesting property of mature NK cells for adoptive cell therapy is that they can be transplanted into a new surrounding with different MHC expression patterns without losing their function [23, 24]. In great contrast to T lymphocytes, NK cells do not induce graft-versus-host disease but rather play a regulatory role in most cases (reviewed in ). With the development of genetic modification technologies, NK cells have been demonstrated they can be further tailored, including the introduction of CARs and knockout of inhibitory genes . Using such techniques, NK cells from patients with hematologic malignancies can swiftly kill autologous tumor cells that were previously resistant to killing by the same NK cells without a CAR [11, 27]. Preclinical studies with CAR-NK cells unraveled in vivo activity similar to that of CAR-T cells in xenograft murine models. Interestingly, the CAR-NK groups show less cytokine release and better overall survival rates [28, 29]. A first CAR-NK study in men showed a promising anti-tumor response without the development of major toxic effects, such as cytokine release storm (CRS) and graft-versus-host disease (GVHD) . These encouraging results pave the way for further development of CAR-NK as an attractive modality for cancer therapy .
In this review, we summarize information from preclinical and clinical studies, reporting on 72 CAR-NK cell line and 35 primary CAR-NK cell investigations. We try to interpret the paradigm for CAR-NK by focusing the design of a CAR and engineering of NK cells. We describe in detail the structure of the CAR, several detection methods of the CAR on the NK cells, the ideal NK cell source for CAR-NK therapy and the techniques for ex vivo expansion of NK cells. We also discuss the approaches to deliver the CAR-containing transgene to NK cells and the methods that have been used to enhance the transduction efficiency. Finally, we will provide a comprehensive outlook on how future CAR-NK-based therapies can be used to eradicate cancer.
In a direct comparison between the CD28 and CD8α hinge domains, it was found that CD28 hinge domains are more likely to promote dimerization of CAR molecules . As a result, the activation stimulus derived from CD28 hinge-bearing CARs is stronger . While this may be beneficial, this could also induce cytokine release syndrome, one of the most severe side effects of CAR-based therapy. Indeed, in a clinical study aiming to improve the safety of anti-CD19-CAR-T therapy, it was found that an optimized CD8α hinge region, together with other modifications, importantly improved the safety profile of the therapy . 041b061a72