Publications by authors named "Zachary Spencer Dunn"

Article Synopsis
  • Cancer immunotherapy using autologous CAR T cells is complicated by manufacturing and patient selection issues, but 'off-the-shelf' options like allogeneic CAR-NKT cells could simplify the process.
  • Researchers developed a new method to produce high-yield IL-15-enhanced CAR-NKT cells that target multiple cancers, showing effectiveness in battling multiple myeloma and removing immunosuppressive cells from tumors.
  • The CAR-NKT cells demonstrated a stable hypoimmunogenic profile, meaning they are less likely to cause harmful immune reactions, making them promising candidates for clinical use without severe side effects like graft versus host disease.
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Article Synopsis
  • Allogeneic Vγ9Vδ2 T cells show promise for cancer therapy due to their safety and tumor-fighting abilities, but their clinical effectiveness has been limited by donor variability and other factors.
  • Researchers are enhancing these T cells by selecting donors based on a biomarker (CD16), which improves their immune response and functionality, supported by RNA sequencing.
  • Preclinical studies in ovarian cancer models confirm that these engineered CD16 Vδ2 T cells are effective, safe, and persist within the body, making them a potential new therapy for treating cancer.
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Advances in cell-based therapy, particularly CAR-T cell therapy, have transformed the treatment of hematological malignancies. Although an important step forward for the field, autologous CAR-T therapies are hindered by high costs, manufacturing challenges, and limited efficacy against solid tumors. With ongoing progress in gene editing and culture techniques, engineered stem cells and their application in cell therapy are poised to address some of these challenges.

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Allo-HSCT is a curative therapy for hematologic malignancies owing to GvL effect mediated by alloreactive T cells; however, the same T cells also mediate GvHD, a severe side effect limiting the widespread application of allo-HSCT in clinics. Invariant natural killer T (iNKT) cells can ameliorate GvHD while preserving GvL effect, but the clinical application of these cells is restricted by their scarcity. Here, we report the successful generation of third-party HSC-engineered human iNKT (HSC-iNKT) cells using a method combining HSC gene engineering and HSC differentiation.

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Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored.

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The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation. Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration. This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and γδT cells.

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Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability.

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Article Synopsis
  • New COVID-19 treatments are urgently needed due to rising cases and new strains threatening vaccine effectiveness, with cell therapy, specifically iNKT cells, showing promise in tackling the disease.
  • Researchers developed a method to produce allogeneic HSC-engineered iNKT cells, enhancing their availability for treatment through engineered hematopoietic stem cells and culture techniques.
  • Preclinical results indicate that these engineered cells resemble natural iNKT cells, effectively kill SARS-CoV-2 infected cells, reduce inflammation, and are safe for use without causing graft-versus-host disease (GvHD).
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Cell-based cancer immunotherapy has revolutionized the treatment of hematological malignancies. Specifically, autologous chimeric antigen receptor-engineered T (CAR-T) cell therapies have received approvals for treating leukemias, lymphomas, and multiple myeloma following unprecedented clinical response rates. A critical barrier to the widespread usage of current CAR-T cell products is their autologous nature, which renders these cellular products patient-selective, costly, and challenging to manufacture.

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The COVID-19 crisis has taken a significant toll on human life and the global economy since its start in early 2020. Healthcare professionals have been particularly vulnerable because of the unprecedented shortage of Facepiece Respirators (FPRs), which act as fundamental tools to protect the medical staff treating the coronavirus patients. In addition, many FPRs are designed to be disposable single-use devices, creating an issue related to the generation of large quantities of non-biodegradable waste.

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