scholarly journals ENHANCING THE POTENCIES OF CHIMERIC ANTIGEN RECEPTOR T CELL (CAR T CELL) BY CRISPR/CAS9 SYSTEM TO ERADICATE RETINOBLASTOMA

2020 ◽  
Vol 3 (2) ◽  
pp. 73-82
Author(s):  
Yehuda Tri Nugroho Supranoto ◽  
Muhammad Yuda Nugraha ◽  
Astuti Setyawardani
Keyword(s):  
T Cell ◽  
Cancer Cells ◽  
Chimeric Antigen Receptor ◽  
Immune Cells ◽  
Antigen Receptor ◽  
Car T Cell ◽  
Programmed Death ◽  
Car T ◽  
Engineered T Cells ◽  
Specific Antigens

Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. There is no therapies that can eradicate specifically the whole cancer cells without any side effects. The disialoganglioside 2 (GD2), one of the cancer’s cell markers that can be treated using immunotherapy, is expressed in RB. Through this fact, immunotherapy based on chimeric antigen receptor (CAR)-engineered T cells targeting cancer-specific antigens has shown great potential in treating this cancer. Although in recent studies show that immune cells are not able to destroy cancer cells because in every cancer cells there is protein programmed death ligand 1 (PD-L1). This literature review also shows the potential technology using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated protein (Cas9) method to silence PD-1 in CAR T cell, so PD-L1 can not deactivate CAR T Cell through PD-1 signaling. The combination using CAR T cell and CRISPR-Cas9 will be the great therapy to eradicate RB without any side effect.

scholarly journals Targeting cancer cells: from historic methods to modern chimeric antigen receptor (CAR) T-Cell strategies

2020 ◽  
Vol 4 (2) ◽  
pp. 32-49
Author(s):  
Kochar Kh. Saleh ◽  
◽  
Semih Dalkiliç ◽  
Lutfiya Kadioğlu Dalkiliç ◽  
Bahra R. Hamarashid ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Cells ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Car T Cell ◽  
Car T

scholarly journals Genome Editing as a Vehicle to Drive Successful Chimeric Antigen Receptor T Cell Therapies to the Clinic

2021 ◽  
Author(s):  
Caitlin R Hopkins ◽  
Joseph A Fraietta
Keyword(s):  
T Cell ◽  
Genome Editing ◽  
Chimeric Antigen Receptor ◽  
Gene Editing ◽  
Antigen Receptor ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T ◽  
Specific Antigens

Chimeric antigen receptor (CAR) T cells have emerged as an effective therapy for patients with relapsed and refractory haematological malignancies. However, there are many challenges preventing clinical efficacy and thus broader translation of this approach. These hurdles include poor autologous T cell fitness, manufacturing issues and lack of conserved tumour-restricted antigens to target. Recent efforts have been directed toward incorporating genome editing technologies to address these challenges and develop potent CAR T cell therapies for a diverse array of haematopoietic cancers. In this review, the authors discuss gene editing strategies that have been employed to augment CAR T cell fitness, generate allogeneic ‘off-the-shelf’ CAR T cell products, and safely target elusive myeloid and T cell cancers that often lack appropriate tumour-specific antigens.

scholarly journals T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6067
Author(s):  
Elien De Bousser ◽  
Nico Callewaert ◽  
Nele Festjens
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
The Us ◽  
Specific Antigens

In the past decade, chimeric antigen receptor (CAR) T cell technology has revolutionized cancer immunotherapy. This strategy uses synthetic CARs to redirect the patient’s own immune cells to recognize specific antigens expressed on the surface of tumor cells. The unprecedented success of anti-CD19 CAR T cell therapy against B cell malignancies has resulted in its approval by the US Food and Drug Administration (FDA) in 2017. However, major scientific challenges still remain to be addressed for the broad use of CAR T cell therapy. These include severe toxicities, limited efficacy against solid tumors, and immune suppression in the hostile tumor microenvironment. Furthermore, CAR T cell therapy is a personalized medicine of which the production is time- and resource-intensive, which makes it very expensive. All these factors drive new innovations to engineer more powerful CAR T cells with improved antitumor activity, which are reviewed in this manuscript.

scholarly journals A Comprehensive Review of Recent Advancements in Cancer Immunotherapy and Generation of CAR T Cell by CRISPR-Cas9

Processes ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 16
Author(s):  
Md. Al Saber ◽  
Partha Biswas ◽  
Dipta Dey ◽  
Md. Abu Kaium ◽  
Md. Aminul Islam ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T ◽  
Engineered T Cells

The mechanisms involved in immune responses to cancer have been extensively studied for several decades, and considerable attention has been paid to harnessing the immune system’s therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell cancer therapy and CAR T-cell therapy have gained prominence through immunotherapy. However, the full potential of cancer immunotherapy remains to be accomplished. In spite of having startling aspects, cancer immunotherapies have some difficulties including the inability to effectively target cancer antigens and the abnormalities in patients’ responses. With the advancement in technology, this system has changed the genome-based immunotherapy process in the human body including the generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR T-cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against cancer. In this review, we have broadly focused on recent immunotherapeutic techniques against cancer and the use of CRISPR-Cas9 technology for the modification of the T cell, which can specifically recognize cancer cells and be used as immune-therapeutics against cancer.

scholarly journals The Advance Cancer Immunotherapy Techniques and the Future Perspective of Modified T Cell Therapy

2021 ◽  
Author(s):  
Md. Al Saber ◽  
Partha Biswas ◽  
Dipta Dey ◽  
Md. Abu Kaium ◽  
Md. Aminul Islam ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T ◽  
Engineered T Cells

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Chimeric antigen receptor T cells immunotherapy: challenges and opportunities in hematological malignancies

Immunotherapy ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 1341-1357
Author(s):  
Nashwa El-Khazragy ◽  
Sherief Ghozy ◽  
Passant Emad ◽  
Mariam Mourad ◽  
Diaaeldeen Razza ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Challenges And Opportunities

Taking advantage of the cellular immune system is the mainstay of the adoptive cell therapy, to induce recognition and destruction of cancer cells. The impressive demonstration of this principle is chimeric antigen receptor-modified T (CAR-T)-cell therapy, which had a major impact on treating relapsed and refractory hematological malignancies. Despite the great results of the CAR-T-cell therapy, many tumors are still able to avoid immune detection and further elimination, as well as the possible associated adverse events. Herein, we highlighted the recent advances in CAR-T-cell therapy, discussing their applications beneficial functions and side effects in hematological malignancies, illustrating the underlying challenges and opportunities. Furthermore, we provide an overview to overcome different obstacles using potential manufacture and treatment strategies.

scholarly journals Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects

2020 ◽  
Author(s):  
Javad Masoumi ◽  
Abdollah Jafarzadeh ◽  
Jalal Abdolalizadeh ◽  
Haroon Khan ◽  
Jeandet Philippe ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Therapy ◽  
Cancer Stem Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Invasive Fungal Infections after Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy: State of the Evidence and Future Directions

2021 ◽  
Vol 7 (2) ◽  
pp. 156
Author(s):  
Will Garner ◽  
Palash Samanta ◽  
Ghady Haidar
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Fungal Infections ◽  
Antigen Receptor ◽  
Invasive Fungal Infections ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes.

scholarly journals Continuous Telemetry Monitoring in Chimeric Antigen Receptor (CAR) T-Cell Therapy Patients

2021 ◽  
Vol 27 (3) ◽  
pp. S211-S212
Author(s):  
Eddie Stephens ◽  
Ansh Mehta ◽  
Tanya Persoon ◽  
Shannon Baker ◽  
Remy David ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

OP206 Expert Elicitation Of Probabilistic Distributions to Inform Survival Modelling of CD19 Chimeric Antigen Receptor T-Cell Therapies

2020 ◽  
Vol 36 (S1) ◽  
pp. 3-3
Author(s):  
Niamh Carey ◽  
Conor Hickey ◽  
Laura Mc Cullagh ◽  
Michael Barry
Keyword(s):  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Expert Elicitation ◽  
Cell Transplant ◽  
Major Advance ◽  
Cell Therapies ◽  
Risk Of Death ◽  
Car T Cell ◽  
Car T

IntroductionIn 2018, the National Centre for Pharmacoeconomics (NCPE) was commissioned to conduct a health technology assessment (HTA) of one of the first commercially available chimeric antigen receptor (CAR) T-cell therapies, tisagenlecleucel. CAR T-cells are a major advance in personalized cancer treatment, demonstrating promising outcomes in relapsed/refractory pediatric acute lymphoblastic leukemia (pALL). However, the results are based on short-term follow up, limiting their value in predicting long-term survival and leading to uncertainty about the most appropriate survival modeling method to employ. This study aimed to address these limitations by means of expert elicitation.MethodsAn expert elicitation method, the histogram technique, was employed. A predefined discrete numerical scale was presented in Microsoft Excel® and the expert was asked to place twenty crosses on a frequency chart. These crosses represented the expert's beliefs about the distribution of particular quantities. Each cross represented five percent of the probabilistic distribution. Individual distributions were then aggregated across experts using linear pooling.ResultsA total of seventeen experts were invited to take part; eight agreed to participate and five completed the exercise. Three experts did not consider tisagenlecleucel to be a “curative” therapy because patients had a higher risk of death, compared with the age- and sex-matched general population. The aggregated distributions indicated the five-year overall survival rate to be thirty-three percent (95% CI 8.65–56.88) in patients who do not receive a subsequent stem cell transplant and twenty percent (95% CI 2.38 -52.04) in those who do.ConclusionsThe results of this study will be used to calibrate CD19 CAR T-cell therapy survival estimates presented in HTA submissions to the NCPE to ensure more robust assessments. They will also be used to inform the construction of a de novo cost-utility model for examining the cost effectiveness of CD19 CAR T-cell therapies for relapsed/refractory pALL in the Irish healthcare setting.

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