scholarly journals 475. Emozolomide Inhibits the Migration of Immune Cells into the Brain Tumor Microenvironment and Their Systemic Expansion, but Exerts a Synergistic Anti-Tumor Effect When Combined with Combined Conditional Cytotoxic/Immune-Gene Therapy

2010 ◽  
Vol 18 ◽  
pp. S183
Keyword(s):  
Gene Therapy ◽  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Gene ◽  
The Brain

scholarly journals IMMU-39. RNA LOADED LIPID-NANOPARTICLES FUNCTION AS CUSTOMIZABLE IMMUNOTHERAPEUTIC VEHICLES AGAINST MALIGNANT GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi127-vi127
Author(s):  
Adam Grippin ◽  
Brandon Wummer ◽  
Hector Mendez-Gomez ◽  
Brian Stover ◽  
Jianping Huang ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Lipid Nanoparticles ◽  
Lymphoid Organs ◽  
Innate Immune ◽  
T Cell Immunity ◽  
Innate Immune Cells ◽  
Cell Immunity ◽  
The Brain

Abstract BACKGROUND While dendritic cell (DC) vaccine therapy has shown considerable promise for glioblastoma (GBM) patients (Mitchell et al. Nature, 2015), their advancement into human clinical trials has been fraught with challenges in the development, manufacturing, and marketing of successful cancer immunotherapies. To circumvent the challenges associated with cell therapy, we have developed a new platform technology consisting of tumor derived mRNA complexed into lipid-nanoparticles (RNA-NPs) for systemic delivery to DCs in vivo and induction of antigen specific T cell immunity against GBM. OBJECTIVES/ METHODS We sought to assess if surface and charge modifications to our custom lipid-NP could facilitate its localization to lymphoid organs and the brain tumor microenvironment. RESULTS We demonstrate that intravenous administration of our unmodified custom RNA-NPs mediate systemic activation of DCs; these include activation of CD11c+ cells in the brains of animals with intact blood brain-barriers (BBBs). RNA-NPs mediate antigen specific T cell immunity and anti-tumor efficacy with increased tumor infiltrating lymphocytes against a NF-1/p53 mutant glioma that recapitulates features of human GBM in immunocompetent mice. Modification of surface charge could direct these RNA-NPs to lymphoid organs (e.g. spleen, lymph nodes) while modification of the lipid backbone (with cholesterol) enhances localization to innate immune cells in NF-1/p53 mutant and GL261 gliomas. We therefore assessed if this customizable lipid-NP could be leveraged for delivery of immune checkpoint inhibitors (ICIs) (i.e. PD-L1 siRNA) to the brain tumor microenvironment. Compared with scrambled siRNA-NPs in combination with ICIs, surface modified siRNA-NPs (antagonizing PD-L1) in combination with ICIs mediated significant antitumor efficacy with 37% long term survivors in an otherwise fatal brain tumor model. CONCLUSION We designed multifunctional RNA-NPs with a simple, scalable synthesis method that enables delivery of nucleic acids to innate immune cells in lymphoid organs and brain tumors.

scholarly journals TMIC-12. TUMOR-HOMING RNA-NANOPARTICLES REPROGRAM IMMUNE CELLS IN THE BRAIN TUMOR MICROENVIRONMENT

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi258-vi258
Author(s):  
Adam Grippin ◽  
Hector Mendez-Gomez ◽  
Brandon Wummer ◽  
Tyler Wildes ◽  
Kyle Dyson ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Tumor Homing ◽  
The Brain

ROS-responsive nanomedicine: Towards targeting the breast tumor microenvironment

2020 ◽  
Vol 28 ◽  
Author(s):  
RamaRao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Reactive Oxygen Species ◽  
Gene Therapy ◽  
Drug Resistance ◽  
Molecular Imaging ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Breast Tumor ◽  
Imaging Techniques ◽  
Oxygen Species ◽  
Massive Accumulation

: The breast tumor microenvironment (TME) promotes drug resistance through an elaborated interaction of TME components mediated by reactive oxygen species (ROS). Despite a massive accumulation of data concerning the targeting the ROS, but little is known about the ROS-responsive nanomedicine for targeting breast TME. This review submits the ROS landscape in breast TME, including ROS biology, ROS mediated carcinogenesis, reprogramming of stromal and immune cells of TME. We also discussed ROS-based precision strategies for imaging TME, including molecular imaging techniques with advanced probes, multiplexed methods, and multi-omic profiling strategies. ROS-responsive nanomedicine also describes various therapies, such as chemo-dynamic, photodynamic, photothermal, sono-dynamic, immune, and gene therapy for BC. We expound ROS-responsive primary delivery systems for chemotherapeutics, phytochemicals, and immunotherapeutics. This review also presents recent updates on nano-theranostics for simultaneous diagnosis and treatment of BCs. We assume that review on this advancing field will be beneficial to the development of ROS-based nanotheranostics for BC.

Immune gene therapy of experimental mouse brain tumor with adenovirus-mediated gene transfer of murine interleukin-4

2000 ◽  
Vol 49 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Koichi Yoshikawa ◽  
Koji Kajiwara ◽  
Makoto Ideguchi ◽  
Tetsuya Uchida ◽  
Haruhide Ito
Keyword(s):  
Gene Therapy ◽  
Brain Tumor ◽  
Gene Transfer ◽  
Mouse Brain ◽  
Interleukin 4 ◽  
Immune Gene ◽  
Experimental Mouse

IMMU-14. REVEALING THE MANY MYELOID STATES IN HUMAN BRAIN TUMORS AND WAYS TO PERTURB THEM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi94-vi95
Author(s):  
Tyler Miller ◽  
Chadi El Farran ◽  
Julia Verga ◽  
Charles Couturier ◽  
Zeyu Chen ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Ex Vivo ◽  
Myeloid Cells ◽  
Human Tumor ◽  
Myeloid Cell ◽  
Low Grade ◽  
Tumor Patients ◽  
The Many

Abstract Recent breakthroughs in immunotherapy have revolutionized treatment for many types of cancer, but unfortunately trials of these therapies have failed to provide meaningful life-prolonging benefit for brain tumor patients, potentially due to abundant immunosuppressive myeloid cells in the tumor. Our ultimate goal is to reprogram immunosuppressive tumor associated myeloid cells to an antitumor state to enable effective immunotherapy. Towards this goal, we have deeply characterized the immune microenvironment of more than 50 primary high and low grade gliomas using high-throughput single-cell RNA-sequencing to reveal recurrent myeloid cell states and immunosuppressive programs across IDH1 wild-type and mutant tumors. We have also established a brain tumor organoid model from primary patient tissue that maintains all of the tumor microenvironment, including myeloid and other immune cells. We utilize the this model to functionally test data-driven reprogramming strategies and understand how they impact the states of tumor and immune cells in the ex vivo human tumor microenvironment.

Recent advancements in brain tumor targeting using magnetic nanoparticles

2020 ◽  
Vol 11 (2) ◽  
pp. 97-112 ◽  
Author(s):  
Himanshu Gandhi ◽  
Abhishek Kumar Sharma ◽  
Shikha Mahant ◽  
Deepak N Kapoor
Keyword(s):  
Gene Therapy ◽  
Brain Tumor ◽  
Magnetic Nanoparticles ◽  
Biomedical Applications ◽  
Tumor Targeting ◽  
Chemotherapeutic Agents ◽  
Diagnostic Systems ◽  
Hyperthermia Treatment ◽  
Recent Developments ◽  
The Brain

Transport of drugs through the blood–brain barrier to the brain and the toxic effects of drugs on the healthy cells can limit the effectiveness of chemotherapeutic agents. In recent years, magnetic nanoparticles (MNPs) have received much attention as targeted therapeutic and diagnostic systems due to their simplicity, ease of preparation and ability to tailor their properties such as their composition, size, surface morphology, etc. for biomedical applications. MNPs are utilized in drug delivery, radio therapeutics, hyperthermia treatment, gene therapy, biotherapeutics and diagnostic imaging. The present review will address the challenges in brain tumor targeting and discuss the application and recent developments in brain tumor targeting using MNPs.

scholarly journals Engineering the Brain Tumor Microenvironment Enhances the Efficacy of Dendritic Cell Vaccination: Implications for Clinical Trial Design

2011 ◽  
Vol 17 (14) ◽  
pp. 4705-4718 ◽  
Author(s):  
Yohei Mineharu ◽  
Gwendalyn D. King ◽  
AKM G. Muhammad ◽  
Serguei Bannykh ◽  
Kurt M. Kroeger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Brain Tumor ◽  
Dendritic Cell ◽  
Tumor Microenvironment ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Dendritic Cell Vaccination ◽  
The Brain

scholarly journals Myeloid Immune Cells CARriying a New Weapon Against Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Rodrigo Nalio Ramos ◽  
Samuel Campanelli Freitas Couto ◽  
Theo Gremen M. Oliveira ◽  
Paulo Klinger ◽  
Tarcio Teodoro Braga ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Immune Cells ◽  
Scientific Community ◽  
Immune Cell ◽  
Clinical Results ◽  
Mononuclear Phagocytes ◽  
Soluble Factors

Chimeric antigen receptor (CAR) engineering for T cells and natural killer cells (NK) are now under clinical evaluation for the treatment of hematologic cancers. Although encouraging clinical results have been reported for hematologic diseases, pre-clinical studies in solid tumors have failed to prove the same effectiveness. Thus, there is a growing interest of the scientific community to find other immune cell candidate to express CAR for the treatment of solid tumors and other diseases. Mononuclear phagocytes may be the most adapted group of cells with potential to overcome the dense barrier imposed by solid tumors. In addition, intrinsic features of these cells, such as migration, phagocytic capability, release of soluble factors and adaptive immunity activation, could be further explored along with gene therapy approaches. Here, we discuss the elements that constitute the tumor microenvironment, the features and advantages of these cell subtypes and the latest studies using CAR-myeloid immune cells in solid tumor models.

scholarly journals The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy

2020 ◽  
Vol 21 (19) ◽  
pp. 7358
Author(s):  
Fiona A. Desland ◽  
Adília Hormigo
Keyword(s):  
T Cells ◽  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Modulation ◽  
Primary Brain Tumor ◽  
Cellular Heterogeneity ◽  
Checkpoint Molecule ◽  
Engineered T Cells ◽  
Immunosuppressive Tumor Microenvironment ◽  
The Brain

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an effective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment.

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