Promising Chimeric Antigen Receptors for Non-B-Cell Hematological Malignancies, Pediatric Solid Tumors, and Carcinomas

2020 ◽  
pp. 137-163
Author(s):  
Jacob S. Appelbaum ◽  
Navin Pinto ◽  
Rimas J. Orentas
Keyword(s):  
B Cell ◽  
Solid Tumors ◽  
Hematological Malignancies ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Pediatric Solid Tumors

scholarly journals Strategies to Improve Chimeric Antigen Receptors Therapies for Neuroblastoma

2020 ◽  
Author(s):  
Piamsiri Sawaisorn ◽  
Korakot Atjanasuppat ◽  
Usanarat Anurathapan ◽  
Somchai Chutipongtanate ◽  
Suradej Hongeng
Keyword(s):  
Solid Tumors ◽  
Immune Cells ◽  
Inadequate Response ◽  
Antigen Receptors ◽  
Antigen Specificity ◽  
Chimeric Antigen Receptors ◽  
Promising Candidate ◽  
Therapeutic Efficiency ◽  
Pediatric Solid Tumors

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

scholarly journals Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 753
Author(s):  
Piamsiri Sawaisorn ◽  
Korakot Atjanasuppat ◽  
Usanarat Anurathapan ◽  
Somchai Chutipongtanate ◽  
Suradej Hongeng
Keyword(s):  
Solid Tumors ◽  
Present State ◽  
Chimeric Antigen Receptor ◽  
Immune Cells ◽  
Inadequate Response ◽  
Antigen Receptors ◽  
Antigen Specificity ◽  
Chimeric Antigen Receptors ◽  
Promising Candidate ◽  
Pediatric Solid Tumors

Chimeric antigen receptors (CARs) are among the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastomas, the most common extracranial pediatric solid tumors with diverse characteristics, could be a promising candidate for using CAR therapies. Several methods harness CAR-modified cells in neuroblastoma to increase therapeutic efficiency, although the assessment has been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reasons behind the inadequate response against neuroblastoma of CAR-modified cells are still not well understood. It is essential to update the present state of comprehension of CARs to improve the efficiency of CAR therapies. This review summarizes the crucial features of CARs and their design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently being investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

scholarly journals A Bird’s-Eye View of Cell Sources for Cell-Based Therapies in Blood Cancers

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1333
Author(s):  
Benjamin Motais ◽  
Sandra Charvátová ◽  
Matouš Hrdinka ◽  
Michal Šimíček ◽  
Tomáš Jelínek ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Blood Cancer ◽  
Cell Based Therapy ◽  
Cell Source ◽  
Different Types ◽  
Cell Sources ◽  
The One ◽  
Initial Results

Hematological malignancies comprise over a hundred different types of cancers and account for around 6.5% of all cancers. Despite the significant improvements in diagnosis and treatment, many of those cancers remain incurable. In recent years, cancer cell-based therapy has become a promising approach to treat those incurable hematological malignancies with striking results in different clinical trials. The most investigated, and the one that has advanced the most, is the cell-based therapy with T lymphocytes modified with chimeric antigen receptors. Those promising initial results prepared the ground to explore other cell-based therapies to treat patients with blood cancer. In this review, we want to provide an overview of the different types of cell-based therapies in blood cancer, describing them according to the cell source.

scholarly journals Understanding and Targeting the Wnt/β-Catenin Signaling Pathway in Chronic Leukemia

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
S. Thanendrarajan ◽  
Y. Kim ◽  
I. G. H. Schmidt-Wolf
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Solid Tumors ◽  
Wnt Pathway ◽  
Hematological Malignancies ◽  
Therapeutic Options ◽  
Special Focus ◽  
Chronic Leukemia ◽  
Current State ◽  
Experimental Approaches

It has been revealed that the Wnt/β-catenin signaling pathway plays an important role in the development of solid tumors and hematological malignancies, particularly in B-cell neoplasia and leukemia. In the last decade there have been made experimental approaches targeting the Wnt pathway in chronic leukemia. In this paper we provide an overview about the current state of knowledge regarding the Wnt/β-catenin signaling pathway in chronic leukemia with special focus on therapeutic options and strategies.

scholarly journals Spectrum of Posttransplant Lymphoproliferations in NSG Mice and Their Association With EBV Infection After Engraftment of Pediatric Solid Tumors

2020 ◽  
Vol 57 (3) ◽  
pp. 445-456 ◽  
Author(s):  
Heather Tillman ◽  
Peter Vogel ◽  
Tiffani Rogers ◽  
Walter Akers ◽  
Jerold E. Rehg
Keyword(s):  
B Cell ◽  
Solid Tumors ◽  
Immune Cells ◽  
Pediatric Patients ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Diseases ◽  
Nsg Mice ◽  
Pediatric Solid Tumors ◽  
Human Immune

Pediatric patients receiving solid organ transplants may develop lymphoproliferative diseases, including graft-versus-host disease (GvHD) and posttransplant lymphoproliferative diseases (PTLDs). We characterized lesions in 11 clinically ill NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice that received pediatric-patient-derived solid tumors (PDXs) and developed immunodeficiency-associated lymphoproliferations comparable to GvHD and PTLDs over a period of 46 to 283 days after implantation. Lymphoproliferations were diffusely positive for human-specific biomarkers, including NUMA1, CD45, and CD43, but lacked immunoreactivity for murine CD45. Human immune cells were CD3-positive, with subsets having immunoreactivity for CD4 and CD8 as well as PAX5, CD79a, and IRF4, resulting from populations of human T and B cells present within the xenotransplants. Tissues and organs infiltrated included mucocutaneous zones (oral cavity and perigenital and perianal regions), haired skin, tongue, esophagus, forestomach, thyroid, salivary glands, lungs, liver, kidneys, spleen, lymph nodes, bone marrow, and brain. In 4 of 5 mice with PTLD, Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected by in situ hybridization in PAX5+ human B cells associated with the PDX ( n = 1/4) or with engrafted human immune cells at other anatomic locations ( n = 4/11). One of the 4 mice had an EBV-associated human large B-cell lymphoma. NSG mice receiving xenotransplants can develop combinations of GvHD, EBV-driven PTLD, and B-cell lymphoma similar to those occurring in human pediatric patients. Therefore, pediatric xenotransplants should undergo histopathologic and immunohistochemical assessment upon collection to ensure that the specimen is not a lymphoma and does not contain lymphoma cells because these neoplasms can morphologically mimic small round blue cell pediatric solid tumors.

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