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Multiple Defects of Natural Killer Cells in Cancer Patients: Anarchy, Dysregulated Systemic Immunity, and Immunosuppression in Metastatic Cancer
May 5, 2020
Anahid Jewett, Janko Kos, Kawaljit Kaur, Tamara Lah Turnsek, Barbara Breznik, Emanuela Senjor, Paul Wong, Kristin Y. Nguyen,a & Meng-Wei Koa
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA; bThe Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA; cDepartment of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia; dFaculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia; eDepartment of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
ABSTRACT: We have previously demonstrated that natural killer (NK) cells are the main immune effectors that can mediate selection and differentiation of different cancer stem cells and undifferentiated tumors via lysis and secreted or membrane-bound interferon-γ and tumor necrosis factor–α, respectively. This leads to growth inhibition and tumor metastasis curtailment. In this review, we present an overview of our findings on NK cell biology and its significance in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in nonobese diabetic/severe combined immunodeficiency (scid)/interleukin-Rγ– –, humanized–bone-marrow/liver/thymus (hu-BLT) mice, and those of human cancer patients. Moreover, we present recent advances in NK cell expansion and therapeutic delivery and discuss the superiority of allogeneic supercharged NK cells over their autologous counterparts for cancer treatment. We review potential loss of NK cell numbers and function at neoplastic and preneoplastic stages of tumorigenesis as a potential mechanism for pancreatic cancer induction and progression. We believe that NK cells should be placed highly in the armamentarium of tumor immunotherapy due to their indispensable role in targeting cancer stem-like/poorly differentiated tumors and a variety of other key NK cell functions that are discussed in this report, including their role in CD8+ T-cell expansion and targeting gene knockout or dedifferentiated tumors. The combination of allogeneic supercharged NK cells and other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity–inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells and CAR-NK cells, chemotherapeutics, and radiotherapeutic strategies can be used for optimal eradication of tumors.
To Read the Entire Publication Please Visit - http://www.dl.begellhouse.com/journals/2ff21abf44b19838,62b8a7004695c197,3d9b031b6a8cfac3.html
NKore BioTherapeutics is proud to announce that Dr. Anahid Jewett, renowned immunotherapy cancer research scientist, has been honored with the distinguished recognition of being named one of the top 2% of scientists in the world by Stanford University. This prestigious accolade is a testament to Dr. Jewett's exceptional contributions to the field of natural killer (NK) cell therapy for cancer. As the Professor and Director of the tumor immunology laboratory at UCLA School of Medicine and Dentistry, Dr. Jewett has dedicated her career to pioneering advancements in immunotherapy. Her groundbreaking research on the use of NK cells for cancer has significantly impacted the landscape of cancer treatment, offering hope to patients worldwide. With membership in the Johnsson Comprehensive Cancer Center (JCCC) and as a key member of the UCLA Tumor Immunology subgroup, Dr. Jewett has been at the forefront of defining and developing the field of natural killer cell therapy for over 35 years. Her extensive body of work, comprising over 150 publications in leading medical journals, has not only advanced scientific knowledge but has also helped shape the current understanding of NK cell therapy. "Dr. Jewett's dedication to advancing the understanding and application of NK cell therapy in cancer treatment has been truly remarkable," said Greg Brophy, Chief Executive Officer at NKore BioTherapeutics. "Her expertise and groundbreaking research have paved the way for new possibilities in cancer immunotherapy, and we are honored to have her as a leading figure in our field and on our team." At NKore BioTherapeutics, our mission is to revolutionize cancer treatment by harnessing the power of the body's own immune system. Dr. Jewett's pioneering work aligns seamlessly with our commitment to utilizing natural killer cell immunotherapy to treat patients of all ages and various forms of cancer. Through our innovative approach, we aim to empower the body's immune system to combat cancer effectively. Dr. Jewett's recognition by Stanford University serves as a testament to her exceptional contributions to the field of cancer immunotherapy and reinforces NKore BioTherapeutics' dedication to providing cutting-edge treatments for cancer patients. We are proud to celebrate Dr. Jewett's achievements and look forward to continuing our collaboration in advancing the field of natural killer cell therapy.
Our CoFounder and Chief Communications Officer Tracy Ryan had the incredible honor and privilege of being invited back to the White House for the 4th time in just a span of 12 months! On September 22, 2023, Tracy was chosen among a select group of 60+ individuals to attend President Biden's highly-anticipated Childhood Cancer Moonshot Forum. This forum was a momentous gathering where key stakeholders, including parent advocates, clinicians, and visionary leaders spearheading pediatric cancer clinical trials, united under one roof to discuss and identify crucial areas of focus that urgently need to be addressed by the administration and our nation as a whole. Tracy's presence at this forum not only exemplified her deep commitment to the cause but also showcased her and her team's invaluable insights and contributions to the field of childhood cancer research and advocacy. Earlier on that same day, she took the stage on Capitol Hill to speak at the 15th annual Congressional Childhood Cancer Caucus. This prestigious invitation came from none other than Congressman Michael McCaul himself, who chairs the committee. Tracy's was joined by other brilliant research scientists and clinicians who have dedicated their lives to advancing the understanding and treatment of pediatric cancer. But Tracy's involvement in the fight against childhood cancer doesn't end there. In 2022, she also had the privilege of attending the Cancer Moonshot Childhood Cancer Briefing, where she had the opportunity to engage with other experts and share NKore's groundbreaking advancements in the treatment of humans. Tracy's presence at these events demonstrates her unwavering dedication to bringing together government, industry and academia to advance cancer research and NKore's initiatives. The backbone of this week is a highly anticipated, yearly event entitled Curefest. This momentous occasion occurs without fail every single year, attracting a multitude of eager participants and devoted supporters. The event is specifically scheduled to coincide with the month of September, which is internationally recognized as pediatric cancer awareness month. Curefest serves as a beacon of hope and unity, bringing together individuals from all walks of life to raise awareness and funds for this noble cause. From heartwarming stories of survival to inspirational speeches from renowned medical professionals, Curefest offers a diverse range of activities and programs that educate, enlighten, and empower attendees. The impact of Curefest extends far beyond the confines of a single day, as it continues to spark conversations, ignite passion, and drive progress in the fight against pediatric cancer. It is a testament to the unwavering commitment of the organizers and volunteers who work tirelessly to make this event a resounding success. Curefest stands as a shining example of what can be achieved when a community comes together with a shared purpose and a burning desire to make a difference. Year after year, Curefest reminds us all that, together, we have the power to heal, support, and uplift those who need it most.
NKore is pleased to present one of its most recent publications proving a synthetic cannabinoid can target and kill cancer stem cells, the seeds of cancer, and can help repair and boost the Natural Killer Cell system, our main defense against cancer. This publication has been accepted to a high impact cancer journal, Advances in Cancer Biology - Metastasis . Cannabinoid-based drugs have been used as palliative treatments along with conventional therapy for amelioration of side effects of radio- and chemotherapy to reduce nausea and stimulate appetite in cancer patients. Cannabinoids were shown to act through activating cannabinoid receptors, CB1 and CB2. Both of these receptors were shown to be increased on tumor cells of multiple origin including prostate, glioblastoma, hepatocarcinoma, breast, and non-small cell lung cancer. Components of the endocannabinoid system have been shown to have anti-tumor effects by inhibiting the proliferation and inducing cell death through apoptosis. The synthetic cannabinoid used in these experiments, a potent cannabinoid receptor agonist with a chemical structure, was previously reported to mediate anti-tumor effect through inducing caspase-independent apoptosis, in addition to inhibiting migration and invasion of tumors in several studies such as glioblastoma, renal cell carcinoma, hepatocellular carcinoma, osteosarcoma, tumorigenic epidermal tumors, prostate tumors, human Kaposi’s sarcoma tumors, mantle cell lymphoma, melanoma and breast cancers. It was also reported that the cannabinoid synergistically increased the effects of radiotherapy in breast cancer cell lines but not in normal breast epithelium, whereas other cannabinoids such as CBD, nabilone and THC failed to enhance anti-proliferative effects of radiation. Furthermore, the synthetic cannabinoid was shown to reduce tumor burden, lung metastasis and tumor induced angiogenesis in vivo in mouse models of breast cancer, non-small cell lung cancer and non-melanoma skin cancer. THE STORY BEHIND THE RESEARCH Dr. Anahid Jewett originally became interested in cannabis as a cancer treatment in 2018 after first meeting her now partner and NKore co-founder Tracy Ryan. Tracy had been on a 6-year mission at that time to find a cure for her daughter Sophie who was diagnosed with a low-grade brain tumor, Optic Pathway Glioma, in 2013. Sophie had been recognized as a medical miracle many times over by all of her treating physicians by this point. They all believed cannabis played a major role in her unheard of successes in immune function, healing ability, seizure mitigation, and overall response to therapy. Sophie required a second brain surgery in 2018 and her mom Tracy was desperate to find a scientist that could take Sophie's live brain tissue, implant it into mice and use those mice to design a treatment strategy that had the potential of actually curing Sophie. Conventional therapy was not curative and Sophie faced living with this tumor in her brain for the rest of her life, with no understanding of how many more years she would require treatment. When Dr. Jewett learned of Sophie's many successes, she became immediately intrigued and agreed to help Tracy on her mission. After testing Sophie's blood and studying her NK Cell function, Dr. Jewett could not explain what was happening in Sophie's body. Sophie was 6-years old at the time and should have had an immature immune system. She had a brain tumor that should result in a broken NK Cell system, and she was on chemo that should have further debilitated her NK Cell function. Despite these factors, her NKs were functioning at 5x that of any healthy patient Dr. Jewett had studied in her 30+ year career. She knew immediately they were on to something and she requested Tracy bring her more patients. After studying the blood of 29 patients that were on specially designed cannabis protocols from Tracy's former company's line of cannabis tinctures called CannaKids, the findings were undeniable. Cannabinoids were returning NK Cell function in every patient studied, which is a person's number one defense against cancer. After reverse engineering these findings in humanized mice the results were groundbreaking, and the result of NKore's cannabinoid publication described above. This research is what brought Dr. Jewett and Tracy together, and the result was the formation of NKore BioTherapeutics alongside their partners Greg Brophy and Tim Brahm. NKore hopes to further design this synthetic cannabinoid to maximize its cancer killing ability, and bring it to market through FDA approved human trials to be used as a standalone or combination therapy in conjunction with their Supercharged Natural Killer Cell therapeutic.