CRISPR–Cas9 gene editing as a tool for developing immunotherapy for cancer

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Gene Editing ◽  
Genetically Engineered ◽  
Cancer Resistance ◽  
Knock Out ◽  
Tumor Tissues ◽  
Engineered T Cells ◽  
Long Time

T cells following genome editing and transformation might be detectable in peripheral blood and tumor tissues for a long time, even more than a year. The types and diversity of T-cells in peripheral blood and tumor tissues changed following transfusion of genetically modified T-cells, and some highly suspected T-cells targeting cancer cells grew, increasing the proportion of such cells. Moreover, after getting genetically engineered T cells, anticancer cytokine secretion increased. T cells changed by gene editing have certain functions, at least from an immunological standpoint. The first clinical research using the CRISPR–Cas9 gene editing method for cancer resistance is more complicated: Using CRISPR–Cas9 gene editing technology to concurrently knock out, amplify, activate and reinfuse three genes in human immune cells. This therapeutic strategy is more demanding, because the changed immune cells have a wider target scope. The data suggest that the efficacy of gene editing in immune cells was 15–45%, and the modified cells could survive long in the peripheral blood and tumor tissues of patients. After three or four months, some T-cells became central T-cells. These encouraging findings pave the way for future experimental cancer research utilizing CRISPR technology.

scholarly journals Emerging Cellular Therapies for Cancer

2019 ◽  
Vol 37 (1) ◽  
pp. 145-171 ◽  
Author(s):  
Sonia Guedan ◽  
Marco Ruella ◽  
Carl H. June
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
Cancer Therapeutics ◽  
Genetically Engineered ◽  
Patients With Cancer ◽  
Practice Of Medicine ◽  
Engineered T Cells ◽  
T Cell Engineering ◽  
New Applications

Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that engineered immune cells can serve as a powerful new class of cancer therapeutics. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Advances in T cell engineering, genetic editing, the selection of optimal lymphocytes, and cell manufacturing have the potential to broaden T cell–based therapies and foster new applications beyond oncology, in infectious diseases, organ transplantation, and autoimmunity.

scholarly journals Genetically Engineered T-Cells for Malignant Glioma: Overcoming the Barriers to Effective Immunotherapy

2019 ◽  
Vol 9 ◽  
Author(s):  
Pavlina Chuntova ◽  
Kira M. Downey ◽  
Bindu Hegde ◽  
Neil D. Almeida ◽  
Hideho Okada
Keyword(s):  
T Cells ◽  
Malignant Glioma ◽  
Genetically Engineered ◽  
Engineered T Cells

scholarly journals CAR T Cell Therapy’s Potential for Pediatric Brain Tumors

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5445
Author(s):  
Pauline Thomas ◽  
Natacha Galopin ◽  
Emma Bonérandi ◽  
Béatrice Clémenceau ◽  
Sophie Fougeray ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Cell Therapy ◽  
Pediatric Brain Tumors ◽  
Genetically Engineered ◽  
Molecular Techniques ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
Engineered T Cells

Malignant central nervous system tumors are the leading cause of cancer death in children. Progress in high-throughput molecular techniques has increased the molecular understanding of these tumors, but the outcomes are still poor. Even when efficacious, surgery, radiation, and chemotherapy cause neurologic and neurocognitive morbidity. Adoptive cell therapy with autologous CD19 chimeric antigen receptor T cells (CAR T) has demonstrated remarkable remission rates in patients with relapsed refractory B cell malignancies. Unfortunately, tumor heterogeneity, the identification of appropriate target antigens, and location in a growing brain behind the blood–brain barrier within a specific suppressive immune microenvironment restrict the efficacy of this strategy in pediatric neuro-oncology. In addition, the vulnerability of the brain to unrepairable tissue damage raises important safety concerns. Recent preclinical findings, however, have provided a strong rationale for clinical trials of this approach in patients. Here, we examine the most important challenges associated with the development of CAR T cell immunotherapy and further present the latest preclinical strategies intending to optimize genetically engineered T cells’ efficiency and safety in the field of pediatric neuro-oncology.

scholarly journals Distinct changes of in BTLA, ICOS, PD-1, and TIGIT expression on peripheral blood and decidual CD8+ T cells in women with unexplained recurrent spontaneous abortion†

2020 ◽  
Vol 103 (5) ◽  
pp. 1012-1017
Author(s):  
Qianqian Liang ◽  
Lingxia Tong ◽  
Liping Xiang ◽  
Sujuan Shen ◽  
Chenhuan Pan ◽  
...  
Keyword(s):  
T Cells ◽  
Spontaneous Abortion ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Immune Escape ◽  
Recurrent Spontaneous Abortion ◽  
Decidual Tissue ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
The Difference

Abstract The two-way communication between the mother and the fetus is accomplished by immune cells. CD8+ T cells of normal pregnant (NP) women express progesterone receptor (PR). Binding of PR to progesterone (P) and the production of progesterone-induced blocking factor (PIBF) can aid immune escape, which is an important factor in the maternal immune response. We detected the proportion of CD8+ T cells and the expression of the surface costimulatory molecules BTLA, TIGIT, ICOS, and PD-1 in peripheral blood and decidual tissues of women with unexplained recurrent spontaneous abortion (URSA) and in NP women. All patients were at 8 -10 weeks of gestation. The results showed that there was no change in the proportions of CD8+ T cells in peripheral blood and decidual tissues of URSA patients compared to those of NP women. In peripheral blood, compared with the NP group, the URSA group showed decreased expression of BTLA + CD8+ T cells and the difference was statistically significant, but there was no difference between the groups in terms of TIGIT + CD8+, PD-1 + CD8+, and ICOS + CD8+ T cells. There was no change in the levels of TIGIT + CD8+, PD-1 + CD8+, ICOS + CD8+, and BTLA + CD8+ T cells in decidual tissue. These data confirm that the number of CD8+ T cells in peripheral blood and decidual tissue is not the main factor leading to the pathogenesis of URSA, and other immune cells may play an important role in URSA, but this hypothesis needs further exploration and research.

scholarly journals Genetically engineered T cells for the treatment of cancer

2013 ◽  
Vol 273 (2) ◽  
pp. 166-181 ◽  
Author(s):  
M. Essand ◽  
A. S. I. Loskog
Keyword(s):  
T Cells ◽  
Genetically Engineered ◽  
Engineered T Cells

scholarly journals Single-cell Profiling of Immune cells After Neoadjuvant Pembrolizumab and Chemotherapy in ⅢA non-small cell lung cancer (NSCLC)

2021 ◽  
Author(s):  
Xiubao Ren ◽  
Zhenzhen Hui ◽  
Jiali Zhang ◽  
Yulin Ren ◽  
XIAOLING LI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Single Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Responses

Abstract The combination of immune checkpoint inhibitors (ICIs) with chemotherapy (chemoimmunotherapy) in the neoadjuvant setting have achieved favorable clinical benefits in non-small cell lung cancer (NSCLC), but the mechanism of clinical responses remain unclear. To identify factors associated with the clinical outcome, we provide a rich resource of 186,477 individual immune cells from matched multiple immune-relevant tissue sites and peripheral blood of four treatment-naïve and eight neoadjuvant chemoimmunotherapy treated ⅢA NSCLC patients (responders versus non-responders) by single-cell RNA-seq and TCR-seq. We showed that the synergistic increase of B cells and CD4+ T cells are associated with positive therapeutic response of neoadjuvant chemoimmunotherapy. B cell IgG subclasses IgG1 and IgG3 play a critical role in anti-tumor immune response in tumor lesion, and this process was driven by increased IL-21 protein secreted by infiltrated T follicular helper (Tfh) cells after neoadjuvant chemoimmunotherapy. Furthermore, we uncovered several critical events for positive clinical outcome, including the diminished activated TNFRSF4+ regulatory T cells (Tregs), increased LAMP3+ dendritic cells (DCs), high pre-therapy peripheral blood T-cell diversity, and the expansion of intratumoral CD4+ T clones and peripheral CD8+ T clones. In total, our comprehensive study of the single-cell profile of immune cells provide mechanistic insight of clinical responses and identified novel predictive factors and potential therapeutic targets for improving the efficiency of neoadjuvant chemoimmunotherapy in NSCLC.

scholarly journals Application of Droplet Digital PCR for the Detection of Vector Copy Number in Clinical CAR/TCR T-Cell Products

2020 ◽  
Author(s):  
Alex Lu ◽  
Hui Liu ◽  
Rongye Shi ◽  
Yihua Cai ◽  
Jinxia Ma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Copy Number ◽  
Cell Receptor ◽  
Digital Pcr ◽  
Retroviral Vectors ◽  
Genetically Engineered ◽  
Hematopoietic Stem ◽  
Engineered T Cells ◽  
Vector Copy Number

Abstract Background : Genetically engineered T cells have become an important therapy for B-cell malignancies. Measuring the efficiency of vector integration into the T cell genome is important for assessing the potency and safety of these cancer immunotherapies. Methods: A digital droplet polymerase chain reaction (ddPCR) assay was developed and evaluated for assessing the average number of lenti- and retroviral vectors integrated into Chimeric Antigen Receptor (CAR) and T-Cell Receptor (TCR)-engineered T cells. Results: The ddPCR assay consistently measured the concentration of an empty vector in solution and the average number of CAR and TCR vectors integrated into T cell populations. There was a linear relationship between the average vector copy number per cell measured by ddPCR and the proportion of cells transduced as measured by flow cytometry. Similar vector copy number measurements were obtained by different staff using the ddPCR assay, highlighting the assays reproducibility among technicians. Analysis of fresh and cryopreserved CAR-T and TCR engineered T cells yielded similar results. Conclusions: ddPCR is a robust tool for accurate quantitation of average vector copy number in CAR and TCR engineered T-cells. The assay is also applicable to other types of genetically engineered cells including Natural Killer cells and hematopoietic stem cells.

Abstract PR16: Genetically engineered T cells redirected against cancer-associated fibroblasts to potentiate immunotherapeutic effects.

2013 ◽  
Author(s):  
Sunitha Kakarla ◽  
Kevin Chow ◽  
Melinda Mata ◽  
Xiao-Tong Song ◽  
Meng-Fen Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Genetically Engineered ◽  
Cancer Associated Fibroblasts ◽  
Engineered T Cells
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