Therapy Of Malignant Tumors Research Articles

Dermatoscopic and morphological features of some clinical variants of seborrheic keratosis

Objective — to determine medical tactics, trace the relationship and supplement the correlation information between clinical manifestations, dermatoscopic patterns and histological picture of typical and flat variants of seborrheic keratosis (SK).Materials and methods. The studies were conducted in Zaporizhzhya Regional Dermatovenerological Clinical Hospital of Zaporizhzhya Regional Council. 20 persons with seborrheic keratosis were monitored — 14 (70 %) women and 6 (30 %) men aged 41 to 87. The screening included a general, dermatoscopic and pathomorphological examination of the patient.Results and discussion. More often, lesions were localized on the skin of the body — in 10 persons, on face and scalp — in 5, on lateral neck — in 3, less often on upper limbs — in 2 patients. Fitzpatrick’s І phototype was detected in 3 (15 %) persons, ІІ phototype — in 13 (65 %), ІІІ phototype — in 4, which equals to 20 %. Histologically, the acanthotic type of seborrheic keratosis was identified in 14 (70 %), papillomatous and reticular in — 5 and 1 patients, respectively. The dermatoscopic picture of the acanthotic variant is represented by the following criteria: milia­like cysts— in 10 cases, comedo­like openings— in 4, «convoluted cerebriform pattern» — in 5, «moth­eaten» border — in 2, verrucous surface — in 1, papillomatous SK with verrucous, papillary surface — in 1, keratoma with patterns of «finger print» type — in 3 cases. The reticular (adenoid) variant is represented by a symmetrical lesion of dark brown color and round shape up to 0.5 cm in diameter with moth-­eaten borders and milia­-like cysts around the periphery. Conclusions. The variability of the clinical, dermatoscopic, and pathomorphological manifestations of seborrheic keratosis needs further search for new algorithms of therapy and differential diagnosis of malignant skin tumors.

MHD Radiative Blood Flow Embracing Gold Particles via a Slippery Sheet through an Erratic Heat Sink/Source

Cancer remains one of the world’s leading healthcare issues, and attempts continue not only to find new medicines but also to find better ways of distributing medications. It is harmful and lethal to most of its patients. The need to selectively deliver cytotoxic agents to cancer cells, to enhance protection and efficacy, has prompted the implementation of nanotechnology in medicine. The latest findings have found that gold nanomaterials can heal and conquer it because the material is studied such as gold (atomic number 79) which produces a large amount of heat and contribute to the therapy of malignant tumors. The purpose of the present study is to research the consequence of heat transport through blood flow (Casson model) that contains gold particles in a slippery shrinking/stretching curved surface. The mathematical modeling of Casson nanofluid containing gold nanomaterials towards the slippery curved shrinking/stretching surface is simplified by utilizing suitable transformation. Numerical dual solutions for the temperature and velocity fields are calculated by using bvp4c methodology in MATLAB. Impacts of related parameters are investigated in the temperature and velocity distribution. The results indicate that the suction parameter accelerates the velocity in the upper branch solution and decelerates it in the lower branch solution, while the temperature diminishes in both solutions. In addition, the Casson parameter shrinks the thickness of the velocity boundary-layer owing to rapid enhancement in the plastic dynamics’ viscosity. Moreover, the nanoparticle volume fraction accelerates the viscosity of blood as well as the thermal conductivity. Thus, findings suggested that gold nanomaterials are useful for drug moving and delivery mechanisms since the velocity boundary is regulated by the volume fraction parameter. Gold nanomaterials also raise the temperature field, so that cancer cells can be destroyed.

The role of autofluorescence, photodynamic diagnosis and Photodynamic therapy in malignant tumors of the duodenum.

This article presents the current state of knowledge and a review of the literature in terms of the prevalence, etiopathogenesis, differential diagnosis, management, prognosis, and treatment of malignant tumors of the duodenum. The role of autofluorescence and photodynamic diagnosis as an emerging treatment method for rarely o ccurring duodenal malignant neoplasms .. We selected publications which can be found in databases such as The National Center for Biotechnology Information, U.S. National Library of Medicine (PubMed), The American Chemical Society, The American Association of Pharmaceutical Sciences and The American Society for Photobiology and The Canada Institute for Scientific and Technical Information.

Bone-targeting polymer vesicles for simultaneous imaging and effective malignant bone tumor treatment

We present a bone-targeting polymer vesicle with excellent single photon emission computed tomography/computed tomography (SPECT/CT) imaging capability and high antitumor drug delivery efficiency as an integrated platform for the simultaneous diagnosing and treatment of malignant bone tumors. This polymer vesicle can be self-assembled from poly(ε-caprolactone)67-b-poly[(L-glutamic acid)6-stat-(L-glutamic acid-alendronic acid)16] (PCL67-b-P[Glu6-stat-(Glu-ADA)16]), directly in water without the aid of a cosolvent. SPECT/CT dynamically tracked the drug distribution in the bone tumor rabbit models, and the tumor size was significantly reduced from >2.0 cm3 to <0.6 cm3 over 11 days. The pathological analysis demonstrated obvious necrosis and apoptosis of the tumor cells. Overall, this bone-targeting polymer vesicle provides us with a new platform for the combination of real-time diagnosis and therapy of malignant bone tumors.

Fulminant type 1 diabetes: 20years of discovery and development.

Twenty years have passed since the first article on fulminant type 1 diabetes (FT1D) was published. FT1D is characterized by an extremely rapid onset of ketoacidosis, high plasma glucose and, conversely, a near-normal glycosylated hemoglobin level. Digestive or flu-like symptoms frequently precede the onset of ketoacidosis. Patients are usually negative for islet-related autoantibodies, with near-complete destruction of pancreatic β-cells, even at the onset of disease. Massive infiltration of immunocytes (insulitis) can be seen in the islets of patients with new-onset FT1D, but this subsides within a few weeks. Early discovery and development of research on FT1D were carried out in Japan, with some reports from Korea and China. Recently, the recognition of FT1D as an immune-related adverse effect of immune-checkpoint inhibitor therapy for various malignant tumors in some patients has drawn the attention of Western countries. The discovery and successful establishment of FT1D as a disease entity was the product of three essential factors: (1) accumulated research data spanning more than 10years; (2) fortuitous clinical observation; and (3) organization of a dedicated Japanese research committee. We anticipate that continued investigations of FT1D by a new generation of researchers will further elucidate the pathogenesis and yield new therapies.

Injectable and NIR-Responsive DNA-Inorganic Hybrid Hydrogels with Outstanding Photothermal Therapy.

Surgical excision is one of the main treatments for malignant tumors. However, high risk of tumour recurrence is a major challenge. Near-infrared (NIR)-light-induced tumor photothermal therapy has been studied, while its clinical applications are still restricted due to the limited therapeutic effects. To address this, here, a novel NIR-light-responsive and injectable DNA-mediated upconversion and Au nanoparticle hybrid (DNA-UCNP-Au) hydrogel is developed. Due to the confined and concentrated environment induced by the interaction between adjacent DNA strands and UCNP-Au NPs, an ultrastrong photothermal effect is observed. A photothermal efficiency as high as 42.7% is realized in the hydrogel, which is superior to pristine inorganic particles. Upon direct peritumoral injection of the hydrogel and with the treatment of 808nm laser irradiation, tumors are eradicated and no recurrence is observed. Meanwhile, there are no side effects on normal tissues due to the local treatment. Taking advantage of the high phototherapeutic effect, biocompatibility, and flexible operability in this system, a novel approach for malignant tumor therapy is demonstrated.

The evolution of interventional oncology in the 21st century.

Interventional oncology (IO) has proven to be highly efficient in the local therapy of numerous malignant tumors in addition to surgery, chemotherapy, and radiotherapy. Due to the advent of immune-oncology with the possibility of tumor control at the molecular and cellular levels, a system change is currently emerging. This will significantly rule oncology in the coming decades. Therefore, one cannot think about IO in the 21st century without considering immunology. For IO, this means paying much more attention to the immunomodulatory effects of the interventional techniques, which have so far been neglected, and to explore the synergistic possibilities with immuno-oncology. It can be expected that the combined use of IO and immuno-oncology will help to overcome the limitations of the latter, such as limited local effects and a high rate of side-effects. To do this, however, sectoral boundaries must be removed and interdisciplinary research efforts must be strengthened. In case of success, IO will face an exciting future.

Diagnosis and Therapy of Benign and Malignant Tumors of the Conjunctiva

The aim of this paper is to give an overview of different benign and malignant epibulbar tumors. Categories can be made of the age of manifestation (paediatric tumors versus tumors of adults), the originating cell types (squamous cell tumors, melanocytic tumors, lymphomas or germ cell tumors) or genesis (proliferative, infectious or degenerating tumors). Most epibulbar tumors show lesions on the conjunctiva or the cornea. These can be flesh coloured or pigmented efflorescences with leucoplakias or hyperkeratosis. Especially malignant tumors show atypical growth of blood vessels, are often prominent and can have ulcerations or bleeding. In case of tumor growth, change in pigmentations or atypical bleedings a malign tumor can be suspected. The diagnosis should be confirmed using histopathological evaluation after an incisional or excisional biopsy. Molecular pathologic techniques extend the diagnostic tools and have an implication on the therapy of metastatic tumors. Therapeutic options of the malignant tumors (apart from lymphomas) are chirurgical excision preferably with a no touch technique and afterwards an adjuvant therapy consisting of radiation or cryotherapy. A topical chemotherapy with Mitomycin C, 5-Fluorouracil or Interferon α2b can be effective to reduce persisting precancerosis and reduce recurrences. In case of a suspected malignant tumor it is advisable to refer the patient to an ophthalmo-oncologic center to plan and ensure interdisciplinary therapy.

Long non‑coding RNA LUCAT1 contributes to cisplatin resistance by regulating the miR‑514a‑3p/ULK1 axis in human non‑small cell lung cancer.

Drug resistance is a major obstacle in the therapy of malignant tumors, including non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in chemoresistance. The present study aimed to investigate the role of lung cancer-associated transcript 1 (LUCAT1) in cisplatin (DDP) resistance in NSCLC. By using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), it was found that the expression of LUCAT1 was elevated and that of microRNA-514a-3p (miR-514a-3p) was decreased in DDP-resistant NSCLC tissues and cells. Functionally, LUCAT1 upregulation enhanced cisplatin resistance by promoting the viability, autophagy and metastasis, and inhibiting the apoptosis of NSCLC cells, as demonstrated by Cell Counting kit-8 (CCK-8) assay, western blot analysis, Transwell assay and flow cytometric analysis. LUCAT1 was identified as a sponge of miR-514a-3p and uncoordinated-51-like kinase 1 (ULK1) was proven to be a target gene of miR-514a-3p by bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The enhancing effect of miR-514a-3p on cisplatin sensitivity was reversed by the elevation of LUCAT1. ULK1 knockdown suppressed cisplatin resistance, while this effect was attenuated by miR-514a-3p inhibition. Moreover, LUCAT1 positively regulated ULK1 expression by targeting miR-514a-3p. In addition, LUCAT1 knockdown suppressed tumor growth in vivo. On the whole, the findings of the present study demonstrate that LUCAT1 contributes to the resistance of NSCLC cells to cisplatin by regulating the miR-514a-3p/ULK1 axis, elucidating a novel regulatory network in cisplatin resistance in NSCLC.

A Head Start: CAR-T Cell Therapy for Primary Malignant Brain Tumors.

Oncology is the midst of a therapeutic renaissance. The realization of immunotherapy as an efficacious and expanding treatment option has empowered physicians and patients alike. However, despite these remarkable advances, we have only just broached the potential immunotherapy has to offer and have yet to successfully expand these novel modalities to the field of neuro-oncology. In recent years, exciting results in preclinical studies of immune adjuvants, oncolytic viruses, or cell therapy have been met with only fleeting signs of response when taken to early phase trials. Although many have speculated why these innovative approaches result in impaired outcomes, we are left empty-handed in a field plagued by a drought of new therapies. Herein, we will review the recent advances across cellular therapy for primary malignant brain tumors, an approach that lends itself to overcoming the inherent resistance mechanisms which have impeded the success of prior treatment attempts.

ABCG2 influence on the efficiency of photodynamic therapy in glioblastoma cells

BackgroundPhotodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) is a promising novel therapeutic approach in the therapy of malignant brain tumors. 5-ALA occurs as a natural precursor of protoporphyrin IX (PpIX), a tumor-selective photosensitizer. The ATP-binding cassette transporter ABCG2 plays a physiologically significant role in porphyrin efflux from living cells. ABCG2 is also associated with stemness properties. Here we investigate the role of ABCG2 on the susceptibility of glioblastoma cells to 5-ALA PDT. MethodsAccumulation of PpIX in doxycycline-inducible U251MG glioblastoma cells with or without induction of ABCG2 expression or ABCG2 inhibition by KO143 was analyzed using flow cytometry. In U251MG cells, ABCG2 was inducible by doxycycline after stable transfection with a tet-on expression plasmid. U251MG cells with high expression of ABCG2 were enriched and used for further experiments (sU251MG-V). PDT was performed on monolayer cell cultures by irradiation with laser light at 635 nm. ResultsElevated levels of ABCG2 in doxycycline induced sU251MG-V cells led to a diminished accumulation of PpIX and higher light doses were needed to reduce cell viability. By inhibiting the ABCG2 transporter with the efficient and non-toxic ABCG2 inhibitor KO143, PpIX accumulation and PDT efficiency could be strongly enhanced. ConclusionGlioblastoma cells with high ABCG2 expression accumulate less photosensitizer and require higher light doses to be eliminated. Inhibition of ABCG2 during photosensitizer accumulation and irradiation promises to restore full susceptibility of this crucial tumor cell population to photodynamic treatment.

Boron neutron capture therapy for malignant brain tumors.

Boron neutron capture therapy (BNCT) is tumor-selective particle radiation therapy that depends on the nuclear capture and fission reactions. These reactions occur when a non-radioactive boron isotope (10B) is irradiated with low-energy thermal neutrons to yield high linear energy transfer α-particles and lithium-7 nuclei within a limited path length, i.e., an almost one-cell diameter. The 10B-containing cells can then be selectively destroyed by these potent particles. BNCT has been applied in the field of malignant brain tumors for newly diagnosed and recurrent malignant gliomas (chiefly glioblastomas). These clinical applications of BNCT have been performed with reactor-based neutron sources over the past decades. We also applied reactor-based BNCT for 58 newly diagnosed glioblastomas and 68 recurrent malignant gliomas including 52 glioblastomas. In this review article, we summarize the clinical results from the literature concerning BNCT for these high-grade gliomas (including our research). We also applied reactor-based BNCT for 46 cases of recurrent and refractory high-grade meningiomas, and some of the results will be presented herein. In Japan, neutron sources have been shifted from reactors to accelerators. Phase 1 and 2 clinical trials have been performed for recurrent malignant gliomas using accelerator-based neutron sources, and now fortunately, a cyclotron-based neutron generator has been approved as a medical device by Japanese regulatory authority, as the world's first accelerator-based BNCT system for medical use. We also discuss the future prospects of accelerator-based BNCT in hospitals as therapy for malignant brain tumors.

Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy.

Gangliosides are carbohydrate-containing sphingolipids that are widely expressed in normal tissues, making most subtypes unsuitable as targets for cancer therapy. However, the disialoganglioside GD2 subtype has limited expression in normal tissues but is overexpressed across a wide range of tumors. Disialoganglioside GD2 can be considered a tumor-associated antigen and well-suited as a target for cancer therapy. Disialoganglioside GD2 is implicated in tumor development and malignant phenotypes through enhanced cell proliferation, motility, migration, adhesion, and invasion, depending on the tumor type. This provides a rationale for targeting disialoganglioside GD2 in cancer therapy with the development of anti-GD2 monoclonal antibodies and other therapeutic approaches. Anti-GD2 monoclonal antibodies target GD2-expressing tumor cells, leading to phagocytosis and destruction by means of antibody-dependent cell-mediated cytotoxicity, lysis by complement-dependent cytotoxicity, and apoptosis and necrosis through direct induction of cell death. Anti-GD2 monoclonal antibodies may also prevent homing and adhesion of circulating malignant cells to the extracellular matrix. Disialoganglioside GD2 is highly expressed by almost all neuroblastomas, by most melanomas and retinoblastomas, and by many Ewing sarcomas and, to a more variable degree, by small cell lung cancer, gliomas, osteosarcomas, and soft tissue sarcomas. Successful treatment of disialoganglioside GD2-expressing tumors with anti-GD2 monoclonal antibodies is hindered by pharmacologic factors such as insufficient antibody affinity to mediate antibody-dependent cell-mediated cytotoxicity, inadequate penetration of antibody into the tumor microenvironment, and toxicity related to disialoganglioside GD2 expression by normal tissues such as peripheral sensory nerve fibers. Nonetheless, anti-GD2 monoclonal antibody dinutuximab (ch14.18) has been approved by the U.S. Food and Drug Administration and dinutuximab beta (ch14.18/CHO) has been approved by the European Medicines Agency for the treatment of high-risk neuroblastoma in pediatric patients. Clinical trials of anti-GD2 therapy are currently ongoing in patients with other types of disialoganglioside GD2-expressing tumors as well as neuroblastoma. In addition to anti-GD2 monoclonal antibodies, anti-GD2 therapeutic approaches include chimeric antigen receptor T-cell therapy, disialoganglioside GD2 vaccines, immunocytokines, immunotoxins, antibody–drug conjugates, radiolabeled antibodies, targeted nanoparticles, and T-cell engaging bispecific antibodies. Clinical trials should clarify further the potential of anti-GD2 therapy for disialoganglioside GD2-expressing malignant tumors.

Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report

BackgroundIn recent years, immune checkpoint inhibitors have been widely used as a crucial therapy in malignant tumors. Immune checkpoint inhibitors can cause various autoimmune side effects called immune-related adverse events because they generate an exaggerated inflammatory response. Encephalitis associated with atezolizumab has rarely been reported as an immune-related adverse event. A case of encephalitis caused by treatment with atezolizumab is presented.Case presentationA 56-year-old Japanese man with lung cancer previously treated with surgery and chemotherapy was admitted with high fever, consciousness disorder, and motor aphasia. His first atezolizumab treatment was 17 days earlier. Admission brain magnetic resonance imaging with gadolinium enhancement showed no abnormalities. Cerebrospinal fluid showed cell count 20/l, protein 166 mg/dl, glucose 73 mg/dl, and interleukin 6 82.9 pg/ml (normal< 8.7 pg/ml). Atezolizumab-induced encephalitis was diagnosed. His symptoms improved the day after steroid pulse therapy was started. Following steroid pulse therapy, oral prednisolone 30 mg was started and tapered. The cerebrospinal fluid findings normalized on day 14. He was discharged on day 16 without neurological sequelae.ConclusionIn this case of encephalitis associated with atezolizumab, prompt steroid pulse therapy led to a successful response, and the outcome was good. The cerebrospinal fluid level of interleukin 6 reflected the severity of the encephalitis well. Clinicians should be aware of the possibility of encephalitis after initiation of immune checkpoint inhibitors.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network

BackgroundMalignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. Patients and methodsData from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. ResultsWe collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. ConclusionAdjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

Development of the Bispecific Antibody in Fab-scFv Format Based on an Antibody to Human Interferon Beta-1 and Antibody to HER2 Receptor

The development of new therapies for malignant tumors is an urgent task. Currently, the humanized antibody trastuzumab is considered the “gold standard” in the complex treatment of breast tumors with overexpression of HER2, human epidermal growth factor receptor 2. However, in some cases, resistance to the specified preparation is observed. The search for new therapies for HER2-associated tumors seems to be an important area of research. A number of clinical studies are currently underway on the use of human interferon-beta (IFN-beta) in oncology. Most of these studies use viral vectors carrying the interferon-beta gene to reduce the systemic effect of this cytokine. The immunocytokine complex of the bispecific antibody and IFN-beta we developed can also avoid the systemic action of IFN-beta. Part of the development of such a complex is the creation of bispecific antibodies of various formats. Based on the neutralizing B16 antibody to IFN-beta and the trastuzumab (Tz) antibody specific for the HER2 receptor, we obtained various variants of bispecific antibodies in Fab-scFv format. It was shown that the proteins obtained bind and neutralize IFN-beta, and they also bind the HER2 receptor in tumor cell lysates and as a recombinant extracellular domain. Such molecules in the immunocytokine complex can be used as delivery vehicles of IFN-beta to HER2-positive tumor cells.

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: The state of science in medullary thyroid carcinoma: current challenges and unmet needs.

The 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) held in Houston, TX, USA, focused on emerging topics in the pathogenesis and therapy of malignant endocrine tumors associated with MEN syndromes. With MEN-2 syndromes, the most common malignancy is medullary thyroid carcinoma (MTC). In the spirit of the original MEN meeting workshop model, the conference included didactic lectures and interactive working groups of clinicians and researchers focused on the state of science in MTC and ongoing challenges or unmet needs in the understanding of MTC and to develop strategies to address these issues.

Basic Research and Preclinical Evaluation of Photodynamic Therapy (PDT) for Malignant Brain Tumors to Improve Further Clinical Effectiveness

Basic Research and Preclinical Evaluation of Photodynamic Therapy (PDT) for Malignant Brain Tumors to Improve Further Clinical Effectiveness

Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord–Stromal Tumors: A Contemporary Review

Non-epithelial ovarian tumors are heterogeneous and account for approximately 10% of ovarian malignancies. The most common subtypes of non-epithelial ovarian tumors arise from germ cells or sex cord and stromal cells of the gonads. These tumors are usually detected at an early stage, and management includes surgical staging and debulking. When indicated for advanced disease, most respond to chemotherapy; however, options for patients with refractory disease are limited, and regimens can be associated with significant toxicities, including permanent organ dysfunction, secondary malignancies, and death. Targeted therapies that potentially decrease chemotherapy-related adverse effects and improve outcomes for patients with chemotherapy-refractory disease are needed. Here, we review the molecular landscape of non-epithelial ovarian tumors for the purpose of informing rational clinical trial design. Recent genomic discoveries have uncovered recurring somatic alterations and germline mutations in subtypes of non-epithelial ovarian tumors. Though there is a paucity of efficacy data on targeted therapies, such as kinase inhibitors, antibody–drug conjugates, immunotherapy, and hormonal therapy, exceptional responses to some compounds have been reported. The rarity and complexity of non-epithelial ovarian tumors warrant collaboration and efficient clinical trial design, including high-quality molecular characterization, to guide future efforts.

Emerging trends in gene-modified-based chimeric antigen receptor-engineered T-cellular therapy for malignant tumors: The lesson from leukemia to pediatric brain tumors.

In 2017 and 2018, Food and Drug Administration has approved YESCARTA (axicabtagene ciloleucel) and KYMRIAH (tisagenlecleucel), two chimeric antigen receptor (CAR)-engineered T-cell products, for B-cell malignancies. It also marked a watershed moment in the development of immunotherapies for cancer. Despite the successes in adults, it remains clinically applicable only in B-cell acute lymphoblastic leukemia in pediatrics. Notably, multiple clinical trials and recent case reports about childhood central nervous system (CNS) tumors, the leading cause of deaths in children, have emerged and granted promising results. With the growing consideration of the biological responses in the interaction of human immunity, the major technical obstacles such as on-target off-tumor toxicity in widespread solid tumors, antigenic heterogeneity, adaptive resistance, difficult T-cell (CD4/CD8) trafficking, and immunosuppressive environments in CNS are gradually approached and ameliorated. The new spotlights of this review are focusing on current development, and emerging treatments for pediatric CNS tumors integrating molecular research with the mainstream of CAR-T therapeutic strategies to sketch a main axis and pathway forward in the improvement of novel gene-modified-based cellular platform.