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"Abstract" is a form of epigenetic gene therapy that has resulted in novel cancer immunotherapies with complex mechanism control, including chimeric antigen receptor T cells that bind tumor-associated antigens to direct coordinated immune responses. We explore the increasingly complicated field of synthetic-biology treatments in cancer immunotherapy in this essay, as well as recent findings within the framework of immunotherapy research. In doing so, a set of basic modular circuits may be developed as a base on which modular circuits can be fabricated to solve more difficult problems. ".
Source link: https://doi.org/10.1158/2326-6066.cir-21-0769
"Abstract Engineering immune cells designed to combat cancer is a rapidly evolving field. " Tumors can be prevented from attacking immune cells targeted by cancer-specific antigens, impaired trafficking of immune cells to solid tumors, the challenging immune system, and variable antigen abundance and presentation assist tumors in addition. T cells are being engineered to produce specific T-cell receptors in order to overcome these challenges. Given that TCRs are targeting intracellular peptides expressed on tumor MHC molecules, this provides an expanded pool of potential targetable tumor-specific antigens similar to CAR T cells' cell-surface antigens. Also with varying degrees of antigen expression on the tumor and surrounding healthy tissue, the TCR T cell's affinity can be tuned to allow for improved tumor recognition. TCR T-cell therapy's challenges and barriers, as well as ways to prevent these and improve anticancer function and efficacy are addressed herein.
Source link: https://doi.org/10.1158/2326-6066.cir-21-0269
"Briefly, priming blood NK cells with recombinant human IL-12, rhIL-15, and rhIL-18 results in memory-like NK cell differentiation and increased responses against cancer. " HCW9201 and HCW9207 stimulated activation and proliferation of cells, but HCW9207 had reduced IL-18 receptor signaling. HCW9201 stimulation enhanced NK cell metabolic endurance and resulted in the DNA methylation remodeling characteristic of memory-like differentiation. Short-term and memory-like NK cell cytotoxicity and IFN u03b3 production against leukemia targets is similar to that in leukemia patients, as well as equivalent control of leukemia in NSG mice. Similarly, HFPCs address a protein engineering strategy that resolves several issues associated with multisignal receptor engagement on immune cells, and HCW9201-primed NK cells could be used as an effective treatment for tumor therapy, with clinical GMP-like memory cells produced as an excellent alternative to clinical GMP-grade memory-like NK cell culture. ".
Source link: https://doi.org/10.1158/2326-6066.cir-20-1002
"Efforts are ongoing to conduct comprehensive ex vivo analyses of patients's immune landscapes before and during immunotherapy. " Herein, we review the benefits and drawbacks of various noninvasive imaging techniques for measuring T-cell responses at various points in the disease cycle, as well as immunotherapy. We also discuss the possibility of using these imaging techniques in monitoring patient response and predicting prognosis among patients treated with immunotherapy.
Source link: https://doi.org/10.1158/2326-6066.cir-20-0678
In obese mice, "Abstract Antitumor immunity is reduced. " We addressed this by analyzing patient data from a variety of cancer types. We found that following immunotherapy was not accurately predicted by body mass index or serum leptin concentrations. The results of a large association between higher HMOX1 expression and reduced progression-free survival were shown by a strong correlation. HO-1 was shown to as a cause of anti-PD1 immunotherapy resistance by mice models of both melanoma and breast cancer, but also highlighted HO-1 as a vulnerability that could be exploited therapeutically using a small-molecule inhibitor. Our clinical findings have implicated serum ox-LDL as a source of therapeutic resistance in patients with cancer patients, operating as a double-edged sword that simultaneously increased HO-1-mediated tumor cell protection and suppressed HO-1u2013-mediated tumor cell protection. ".
Source link: https://doi.org/10.1158/2326-6066.cir-20-0358
HR, 0. 39 percent; P = 0. 21]. "In cohort A, patients with high PD-1+ CD8+ TCR diversity before ICB treatment showed improved responses to ICB and progression-free survival relative to patients with low ethnicity [6. 4 months vs. 2. 5 months, HR, 0. 39; P = 0. 021]. Patients with elevated PD-1+ CD8+ TCR clonality following ICB therapy had longer PFS than those with reduced clonality. "In addition, TCR richness and clonality in peripheral blood PD-1+ CD8+ T cells may act as noninvasive predictors of patient response to ICB and survival in NSCLC. ".
Source link: https://doi.org/10.1158/2326-6066.cir-19-0398
"We found that a potent nanoparticle-based E7 vaccine, but not a conventional u201d vaccine, caused E7 tumor immunogenu2013specific CD8+ T cells in cervical tumor-u2013bearing mice, but not a traditional u201c liquidu201d vaccine. " Immuno-suppressive barriers can be present in tumor microenvironment, and vaccination alone or in conjunction with anti-PD-1/anti-CTLA4 did not cause tumor formation nor increase CD8+ T cells in the tumor microenvironment, indicating the presence of immune-suppressive barriers. Patients with cervical cancer have poor dendritic cell function, have poor cytotoxic lymphocyte responses, and show an accumulation of myeloid cells in the periphery. Here, we showed that myeloid cells in K14HPV16/H2b mice had potent immunosuppressive activity against antigen-presenting cells and CD8+ T cells, dampening anti-tumor immunity. Our results revealed a correlation between HPV-induced cancers, systemic amplification of myeloid cells, and the adverse effects of myeloid cells on CD8+ T-cell activation and recruitment into the TME.
Source link: https://doi.org/10.1158/2326-6066.cir-19-0315
"Abstract No predictive biomarkers can quickly identify patients with non-u2013small cell lung cancer who will benefit from immune checkpoint inhibitor therapy. " We compared changes in the radiomic consistency of CT patterns both within and outside tumor nodules before and after two to three cycles of ICI therapy. We found that DelRADx patterns could predict ICI therapy response and overall survival among patients with NSCLC. We retrospectively reviewed results obtained from 139 patients with NSCLC at two hospitals, which were divided into a discovery set and two independent validation sets. It was established by the Association of a delta-radiomic risk score with OS. The number of TILs on diagnostic biopsy samples was determined by Perpetumoral Gabor characteristics. Our findings indicate that DelRADx can be used to determine early functional responses in patients with NSCLC.
Source link: https://doi.org/10.1158/2326-6066.cir-19-0476
"The long-term effect of sipuleucel-T on tumor antigen-specific immune responses and B-cell receptor sequences remain unclear," says B-cell responses, as measured by antigen-specific antibody responses and B-cell receptor sequences. " We investigated whether sipuleucel-T could have long-term immunologic memory before and after sipuleucel-T therapy in two groups of patients with mCRPC, those who had previously received sipuleucel-T versus those that did not. To determine whether sipuleucel-T could have prolonged immunologic memory, we compared blood cellscirculating B-cell responses before and after sipuleucel-T therapy in two groups of patients with mCRPC Compared to nau00efve patients, previous patients had persistent antibody responses, as well as more focused and convergent BCR repertoires with distinct VJ gene usage. Patients treated in re-treatment, previously treated patients maintained high-frequency clones and increased more convergent BCRs at earlier time points unlike nau00efve patients. With a steady influx of new B-cell clones, nau00efve patients maintained high BCR turnover in comparison. According to increased clonal maturation, older treated patients had more highly organized B-cell repertoires, consistent with greater clonal maturation. ".
Source link: https://doi.org/10.1158/2326-6066.cir-20-0252
"Abstract Tertiary lymphoid aggregates are ectopic lymphoid aggregates that resemble traditional secondary lymphoid organs and are often found at sites of chronic inflammation. " The presence of tumor-associated TLS has been correlated with longer patient survival, higher incidences of disease-free survival, and a positive reaction to new cancer therapies. Understanding more about TA-TLS design, manufacture, and function may lead to new therapeutic approaches to modulate antitumor immunity. ".
Source link: https://doi.org/10.1158/2326-6066.cir-20-0432
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