scholarly journals Adoptive Cell Therapy—Harnessing Antigen-Specific T Cells to Target Solid Tumours

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 683 ◽  
Author(s):  
Elżbieta Chruściel ◽  
Zuzanna Urban-Wójciuk ◽  
Łukasz Arcimowicz ◽  
Małgorzata Kurkowiak ◽  
Jacek Kowalski ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Cell Therapy ◽  
Solid Tumours ◽  
Great Success ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Cell Therapies ◽  
Alternative Approaches ◽  
Therapeutic Tools ◽  
Infiltrating Lymphocytes

In recent years, much research has been focused on the field of adoptive cell therapies (ACT) that use native or genetically modified T cells as therapeutic tools. Immunotherapy with T cells expressing chimeric antigen receptors (CARs) demonstrated great success in the treatment of haematologic malignancies, whereas adoptive transfer of autologous tumour infiltrating lymphocytes (TILs) proved to be highly effective in metastatic melanoma. These encouraging results initiated many studies where ACT was tested as a treatment for various solid tumours. In this review, we provide an overview of the challenges of T cell-based immunotherapies of solid tumours. We describe alternative approaches for choosing the most efficient T cells for cancer treatment in terms of their tumour-specificity and phenotype. Finally, we present strategies for improvement of anti-tumour potential of T cells, including combination therapies.

scholarly journals Generating CAR T cells from tumor-infiltrating lymphocytes

2021 ◽  
Vol 9 ◽  
pp. 251513552110171
Author(s):  
Jane K. Mills ◽  
Melissa A. Henderson ◽  
Lauren Giuffrida ◽  
Pasquale Petrone ◽  
Jennifer A. Westwood ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Proliferative Potential ◽  
Melanoma Tumor ◽  
Cell Therapies ◽  
Nsg Mice ◽  
Car T ◽  
Infiltrating Lymphocytes

Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. Methods: We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Results: Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen. CAR-TIL produced greater amounts of IFN compared with parental TIL, when co-cultured with Her2 expressing tumor lines, including autologous melanoma tumor lines, although no consistent increase in cytotoxicity by TIL was afforded by expression of a CAR. Results of an in vivo study in NSG mice demonstrated tumor shrinkage when CAR-TILs were used in an adoptive cell therapy protocol. Conclusion: Potential limitations of transduced TIL in our study included limited proliferative potential and a terminally differentiated phenotype, which would need addressing in further work before consideration of clinical translation.

scholarly journals Adoptive Cell Therapy—Tumor-Infiltrating Lymphocytes, T-Cell Receptors, and Chimeric Antigen Receptors

2015 ◽  
Vol 42 (4) ◽  
pp. 626-639 ◽  
Author(s):  
Steven A. Feldman ◽  
Yasmine Assadipour ◽  
Isaac Kriley ◽  
Stephanie L. Goff ◽  
Steven A. Rosenberg
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
T Cell Receptors ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Cell Receptors ◽  
Infiltrating Lymphocytes

scholarly journals Therapeutic Applications of Engineered Chimeric Antigen Receptors-T cell for Cancer Therapy

2021 ◽  
Author(s):  
Amina Hussain
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Malignant Tumors ◽  
Adoptive Cell Therapy ◽  
Clinical Results ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
T Cell Therapy

Findings of new targeted treatments with adequate safety evaluations is essential for better cancer cures and mortality rates. Immunotherapy holds promise for patients with relapsed disease, with the ability to elicit long-term remissions. Emerging promising clinical results in B-cell malignancy using gene-altered T-lymphocytes uttering chimeric antigen receptors have sparked a lot of interest. This treatment could open the path for a major difference in the way we treat tumors that are resistant or recurring. Genetically altered T cells used to produce tumor-specific chimeric antigen receptors are resurrected field of adoptive cell therapy by demonstrating remarkable success in the treatment of malignant tumors. Because of the molecular complexity of chimeric antigen receptors -T cells, a variety of engineering approaches to improve safety and effectiveness are necessary to realize larger therapeutic uses. In this study, we investigate at new strategies for enhancing chimeric antigen receptors-T cell therapy by altering chimeric antigen receptors proteins, T lymphocytes, and their relations with other solid tumor microenvironment (TME) aspects.

scholarly journals Antibody-modified T cells: CARs take the front seat for hematologic malignancies

Blood ◽  
2014 ◽  
Vol 123 (17) ◽  
pp. 2625-2635 ◽  
Author(s):  
Marcela V. Maus ◽  
Stephan A. Grupp ◽  
David L. Porter ◽  
Carl H. June
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Specific Antigen ◽  
Hematologic Malignancies ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Front Seat ◽  
Cell Therapies ◽  
Car T ◽  
Wide Road

Abstract T cells redirected to specific antigen targets with engineered chimeric antigen receptors (CARs) are emerging as powerful therapies in hematologic malignancies. Various CAR designs, manufacturing processes, and study populations, among other variables, have been tested and reported in over 10 clinical trials. Here, we review and compare the results of the reported clinical trials and discuss the progress and key emerging factors that may play a role in effecting tumor responses. We also discuss the outlook for CAR T-cell therapies, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all hematologic malignancies. Many questions remain in the field of CAR T cells directed to hematologic malignancies, but the encouraging response rates pave a wide road for future investigation.

scholarly journals Engineering Chimeric Antigen Receptors

Acta Naturae ◽  
2017 ◽  
Vol 9 (1) ◽  
pp. 6-14 ◽  
Author(s):  
S. V. Kulemzin ◽  
V. V. Kuznetsova ◽  
M. Mamonkin ◽  
A. V. Taranin ◽  
А. A. Gorchakov
Keyword(s):  
T Cells ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Car T Cells ◽  
Car T ◽  
Protein Molecules ◽  
Alternative Approaches ◽  
Anti Tumor Activity

Chimeric antigen receptors (CARs) are recombinant protein molecules that redirect cytotoxic lymphocytes toward malignant and other target cells. The high feasibility of manufacturing CAR-modified lymphocytes for the therapy of cancer has spurred the development and optimization of new CAR T cells directed against a broad range of target antigens. In this review, we describe the main structural and functional elements constituting a CAR, discuss the roles of these elements in modulating the anti-tumor activity of CAR T cells, and highlight alternative approaches to CAR engineering.

scholarly journals Next-generation cell therapies: the emerging role of CAR-NK cells

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 570-578
Author(s):  
Rafet Basar ◽  
May Daher ◽  
Katayoun Rezvani
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Natural Killer ◽  
Γδ T Cells ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells

Abstract T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical, and toxicity issues. Given these concerns, there is a rapidly growing interest in natural killer cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the allogeneic setting. Other immune effector cells, such as invariant natural killer T cells, γδ T cells, and macrophages, are attracting interest as well and eventually may be added to the repertoire of engineered cell therapies against cancer. The pace of these developments will undoubtedly benefit from multiple innovative technologies, such as the CRISPR-Cas gene editing system, which offers great potential to enhance the natural ability of immune effector cells to eliminate refractory cancers.

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