scholarly journals A Review of T-Cell Related Therapy for Osteosarcoma

2020 ◽  
Vol 21 (14) ◽  
pp. 4877
Author(s):  
Kazushige Yoshida ◽  
Masanori Okamoto ◽  
Kaoru Aoki ◽  
Jun Takahashi ◽  
Naoto Saito
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Malignant Tumors ◽  
Checkpoint Inhibitor ◽  
T Cell Response ◽  
The Other ◽  
T Cell Therapy ◽  
Tumors Of Bone ◽  
Better Than

Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.

scholarly journals Cancer immunotherapy: current opportunities and perspectives

2021 ◽  
Vol 4 (2) ◽  
pp. 25-38
Author(s):  
O.Yu. Nikolaeva ◽  
R.V. Liubota ◽  
O.S. Zotov ◽  
R.I. Vereshchako
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Cancer Immunotherapy ◽  
Anticancer Agents ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Tumor Focus

Cancer immunotherapy is a relatively new and pro­mising method of treating neoplasms. Understanding the antigen-directed cytotoxicity of T-lymphocytes has become one of the central directions in involving the immune system in the fight against cancer. Basic research in this area has led to the invention of checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. Cytokines can enhance the action of T-lymphocytes for their ability to directly stimulate effector and stromal cells in tumor focus and enhance recognition of tumor cells by cytotoxic effector cells. They were the first in cancer immunotherapy and remain relevant to this day. Today, immunotherapy is an effective treatment for most malignant tumors, including melanoma, non-small cell lung cancer, liver, stomach, bladder, cervical cancer, some types of breast cancer, lymphoma, etc. However, immunotherapy of some malignant tumors is ineffective, therefore, the development of new and improvement of existing immunotherapy agents is actively underway, and there is a hope that the indications for its use will expand. For this purpose, this review discusses the principles of action of various classes of immunotherapeutic anticancer agents, namely cytokines, immune checkpoint inhibitors, and adaptive T-cell therapy. The work highlights their indications, efficacy and toxicity from the use of each class of drugs, as well as the prospects for the development of immunotherapeutic anticancer drugs.

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 Two is better than one: advances in pathogen-boosted immunotherapy and adoptive T-cell therapy

Immunotherapy ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 837-849 ◽  
Author(s):  
Gang Xin ◽  
David M Schauder ◽  
Ryan Zander ◽  
Weiguo Cui
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Better Than

scholarly journals Early programming of CD8+ T cell response by the orphan nuclear receptor NR4A3

2020 ◽  
Vol 117 (39) ◽  
pp. 24392-24402 ◽  
Author(s):  
Livia Odagiu ◽  
Salix Boulet ◽  
Dave Maurice De Sousa ◽  
Jean-François Daudelin ◽  
Sandrine Nicolas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Nuclear Receptor ◽  
T Cell Activation ◽  
Cell Response ◽  
Adoptive Cell Therapy ◽  
T Cell Response ◽  
Orphan Nuclear Receptor ◽  
T Cell Therapy

Enhancing long-term persistence while simultaneously potentiating the effector response of CD8+ T cells has been a long-standing goal in immunology to produce better vaccines and adoptive cell therapy products. NR4A3 is a transcription factor of the orphan nuclear receptor family. While it is rapidly and transiently expressed following T cell activation, its role in the early stages of T cell response is unknown. We show that NR4A3-deficient murine CD8+ T cells differentiate preferentially into memory precursor and central memory cells, but also produce more cytokines. This is explained by an early influence of NR4A3 deficiency on the memory transcriptional program and on accessibility of chromatin regions with motifs for bZIP transcription factors, which impacts the transcription of Fos/Jun target genes. Our results reveal a unique and early role for NR4A3 in programming CD8+ T cell differentiation and function. Manipulating NR4A3 activity may represent a promising strategy to improve vaccination and T cell therapy.

scholarly journals Clinical efficacy of T-cell therapy after short-term BRAF-inhibitor priming in patients with checkpoint inhibitor-resistant metastatic melanoma

2021 ◽  
Vol 9 (7) ◽  
pp. e002703
Author(s):  
Troels Holz Borch ◽  
Katja Harbst ◽  
Aynal Haque Rana ◽  
Rikke Andersen ◽  
Evelina Martinenaite ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Tumor Biomarker ◽  
Autologous Tumor ◽  
T Cell Therapy

PurposeDespite impressive response rates following adoptive transfer of autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, improvement is needed to increase the efficacy and broaden the applicability of this treatment. We evaluated the use of vemurafenib, a small-molecule BRAF inhibitor with immunomodulatory properties, as priming before TIL harvest and adoptive T cell therapy in a phase I/II clinical trial.Methods12 patients were treated with vemurafenib for 7 days before tumor excision and during the following weeks until TIL infusion. TILs were grown from tumor fragments, expanded in vitro and reinfused to the patient preceded by a lymphodepleting chemotherapy regimen and followed by interleukin-2 infusion. Extensive immune monitoring, tumor profiling and T cell receptor sequencing were performed.ResultsNo unexpected toxicity was observed, and treatment was well tolerated. Of 12 patients, 1 achieved a complete response, 8 achieved partial response and 3 achieved stable disease. A PR and the CR are ongoing for 23 and 43 months, respectively. In vitro anti-tumor reactivity was found in TILs from 10 patients, including all patients achieving objective response. Serum and tumor biomarker analyses indicate that baseline cytokine levels and the number of T cell clones may predict response to TIL therapy. Further, TCR sequencing suggested skewing of TCR repertoire during in vitro expansion, promoting certain low frequency clonotypes.ConclusionsPriming with vemurafenib before infusion of TILs was safe and feasible, and induced objective clinical responses in this cohort of patients with checkpoint inhibitor-resistant metastatic melanoma. In this trial, vemurafenib treatment seemed to decrease attrition and could be considered to bridge the waiting time while TILs are prepared.

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