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Review synthesizes research on NK cells' role in cancer immunity and their potential in therapeutics through bioengineering, immune checkpoint inhibitors, and cell engagers, highlighting ongoing preclinical and clinical trials. Via BigField GEG Tech 
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Chimeric antigen receptor (CAR) T cells, T cells that have been genetically engineered to express a receptor that recognizes a specific antigen, have given rise to breakthroughs in treating hematological malignancies. However, their success in treating solid tumors has been limited. The unique challenges posed to CAR T cell therapy by solid tumors can be described in three steps: finding, entering, and surviving in the tumor. The use of dual CAR designs that recognize multiple antigens at once and local administration of CAR T cells are both strategies that have been used to overcome the hurdle of localization to the tumor. Additionally, the immunosuppressive tumor microenvironment has implications for T cell function in terms of differentiation and exhaustion, and combining CARs with checkpoint blockade or depletion of other suppressive factors in the microenvironment has shown very promising results to mitigate the phenomenon of T cell exhaustion. Finally, identifying and overcoming mechanisms associated with dysfunction in CAR T cells is of vital importance to generating CAR T cells that can proliferate and successfully eliminate tumor cells. The structure and costimulatory domains chosen for the CAR may play an important role in the overall function of CAR T cells in the TME, and “armored” CARs that secrete cytokines and third- and fourth-generation CARs with multiple costimulatory domains offer ways to enhance CAR T cell function.
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This 2-day scientific conference will convene experts in oncology and immunology to discuss emerging approaches, challenges, and opportunities faced in the rapidly evolving field of cancer immunotherapy.
Gilbert C FAURE's insight:
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cancer is approached on https://www.scoop.it/t/immunology-and-biotherapies?q=cancer
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Current Opinion in Immunology Volume 25, Issue 3, June 2013, Pages 389–395
Dendritic cell-based nanovaccines for cancer immunotherapyLeonie E Paulis1,Subhra Mandal1,Martin Kreutz,Carl G FigdorDepartment of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands http://dx.doi.org/10.1016/j.coi.2013.03.001, How to Cite or Link Using DOI Via Alfredo Corell, Anthony M Crasto DR.
Alfredo Corell's curator insight,
July 27, 2013 2:59 PM
Cancer immunotherapy critically relies on the efficient presentation of tumor antigens to T-cells to elicit a potent anti-tumor immune response aimed at life-long protection against cancer recurrence. Recent advances in the nanovaccine field have now resulted in formulations that trigger strong anti-tumor responses. Nanovaccines are assemblies that are able to present tumor antigens and appropriate immune-stimulatory signals either directly to T-cells or indirectly via antigen-presenting dendritic cells. This review focuses on important aspects of nanovaccine design for dendritic cells, including the synergistic and cytosolic delivery of immunogenic compounds, as well as their passive and active targeting to dendritic cells. In addition, nanoparticles for direct T-cell activation are discussed, addressing features necessary to effectively mimic dendritic cell/T-cell interactions. |
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Precision-controlled CAR-T-cell immunotherapies could be used to tackle a range of tumour types. Via BigField GEG Tech
BigField GEG Tech's curator insight,
December 19, 2022 10:39 AM
Researchers have bolstered the power of chimeric antigen receptor (CAR)-T cancer therapies, which use genetically altered T cells to seek out tumours and mark them for destruction. Now scientists have further engineered the cells to contain switches that allow control over when and where the cells are active. This helps them to infiltrate tumours and dodge immune-suppressing defences.
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Therapeutic cancer vaccines have undergone a resurgence in the past decade. A better understanding of the breadth of tumour-associated antigens, the native immune response and development of novel technologies for antigen delivery has facilitated improved vaccine design. The goal of therapeutic cancer vaccines is to induce tumour regression, eradicate minimal residual disease, establish lasting antitumour memory and avoid non-specific or adverse reactions. However, tumour-induced immunosuppression and immunoresistance pose significant challenges to achieving this goal. In this Review, we deliberate on how to improve and expand the antigen repertoire for vaccines, consider developments in vaccine platforms and explore antigen-agnostic in situ vaccines. Furthermore, we summarize the reasons for failure of cancer vaccines in the past and provide an overview of various mechanisms of resistance posed by the tumour. Finally, we propose strategies for combining suitable vaccine platforms with novel immunomodulatory approaches and standard-of-care treatments for overcoming tumour resistance and enhancing clinical efficacy. This Review broadly discusses therapeutic cancer vaccines, covering resistance mechanisms and strategies to overcome these, how to improve the antigen repertoire for vaccines and vaccine platforms, and approaches for enhancing immunotherapy efficacy.
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The first of a promising new class of cancer drugs went on sale in Japan this week at an average annual cost of $143,000 a patient, a harbinger of hefty prices the new drugs are expected to command in the U.S.and Europe in coming months. Bristol-Myers, which plans to market nivolumab in the U.S. if the FDA clears it for sale, declined to say how much it will charge. A spokeswoman said the company prices its medicines based on “the value they deliver to patients and society, the scientific innovation they represent and the investment required to support” drug research-and-development.
Higher prices for new cancer drugs have become an increasing concern for patients and their families, who often shoulder high copayments. At the same time, the PD-1 drugs “have the potential to be game-changers for a lot of people” because patients in studies have had “meaningful, long-term responses” to the drugs. PD-1 targeting drugs have shown strong cancer-fighting results in clinical trials.
Bristol-Myers, which plans to market nivolumab in the U.S. if the FDA clears it for sale, declined to say how much it will charge. A spokeswoman said the company prices its medicines based on “the value they deliver to patients and society, the scientific innovation they represent and the investment required to support” drug research-and-development. Bristol-Myers has been marketing another kind of cancer immunotherapy, Yervoy, as a melanoma treatment in the U.S. since 2011 at a cost of $120,000 a patient for a standard, complete course of treatment. Via Pharma Guy, Krishan Maggon
Pharma Guy's curator insight,
September 5, 2014 1:03 PM
On Quora, I posted the question: "How close are the pharmaceutical companies to "curing" cancer?" (see here) and got some interesting feedback. Dan Munro (@danmunro), Founder / CEO - iPatient, had this to say: "While curing a given cancer is clearly a worthwhile goal - it is often not the primary focus - and early detection is still the leading indicator of successfully treating all cancers. Some cancers are simply pushed so far into remission that you're more likely to die of a different cancer or old age in your sleep. It's not a technical cure - but it's a practical one. So, (1) the reality is that the death rate for cancer hasn't improved very much in the past 50 years, and (2) pharma's little "pills" haven't contributed much to that statistic. Shame on Bayer for taking credit where none is due! 
Krishan Maggon 's curator insight,
September 5, 2014 7:07 PM
High cost of new life saving cancer and HCV drugs. Increasing safety and efficacy bar means limited chances of success and higher costs for the pharma biotech industry due to regulatory burden.
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In a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania School of Medicine show that a two-step personalized immunotherapy treatment — a dendritic cell vaccine using the patient’s own tumor followed by adoptive T cell therapy — triggers anti-tumor immune responses in advanced ovarian cancer patients. Via Alfredo Corell
Alfredo Corell's curator insight,
February 10, 2013 5:55 AM
Most ovarian cancer patients are diagnosed with late stage disease that is unresponsive to existing therapies. In a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania School of Medicine show that a two-step personalized immunotherapy treatment — a dendritic cell vaccine using the patients’ own tumor followed by adoptive T cell therapy — triggers anti-tumor immune responses in these type of patients. Four of the six patients treated in the phase I trial responded to the therapy, the investigators report this month in OncoImmunology.
Direct link to the journal: http://www.landesbioscience.com/journals/oncoimmunology/article/22664/?show_full_text=true& |
In a recent study published in the journal Nature, researchers have compiled the available literature on natural killer (NK) cells, innate immune cells involved in the recognition and elimination of cells in distress, particularly virus-infected cells and tumors. They focus on reviewing current preclinical and clinical research in the field of NK therapies, primarily elucidating the role of NK cells in cancer immunity. They also explore the potential of bioengineering approaches to harness NK cells via the development of genetically modified NK cells, immune checkpoint inhibitors and cell engagement agents. The study reveals that, despite less than two decades of research in the field, NK cells are emerging as a safe, practical and potentially widely accessible means of clinical therapy, particularly antitumor. Although challenges exist in the adoption of NK cell therapies by conventional medicine, studies aimed at overcoming these challenges are already underway, bringing the future of clinical NK cell interventions closer than ever.