scholarly journals Current Mesothelioma Treatment and Future Perspectives

Mesothelioma ◽  
2020 ◽  
Author(s):  
Danijela Štrbac ◽  
Katja Goričar ◽  
Viljem Kovač ◽  
Vita Dolžan
Keyword(s):  
Malignant Mesothelioma ◽  
Treatment Modalities ◽  
T Cell Therapy ◽  
Genetic Characteristics ◽  
New Therapeutic Approaches ◽  
Car T Cell Therapy ◽  
New Frontier ◽  
Car T ◽  
New Treatment ◽  
New Perspective

The established treatments in malignant mesothelioma are based on trimodality approach including surgery, radiation and chemotherapy. Such approach has proved to clinically benefit mesothelioma patients, however the current treatments seem to have reached a limit regarding the survival and disease control. One approach to overcome the limitations of current treatments is focused on finding appropriate serum or genetic biomarkers that could support personalized medicine and improve outcomes with established treatment modalities in mesothelioma patients. The other approach is exploiting better understanding of molecular and genetic characteristics of mesothelioma to search for new treatment modalities. Immunotherapy with anti PD-1, PD-L1 and CTLA-4 agents is a new frontier in mesothelioma treatment. As in many solid tumors, CAR-T cell therapy is emerging from the field of hematological malignancies. Immunomodulatory approaches seem to be a new perspective in treatment of malignant mesothelioma. This chapter aims to explore possible new therapeutic approaches in mesothelioma.

scholarly journals Anti-Mesothelin CAR T cell therapy for malignant mesothelioma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Laura Castelletti ◽  
Dannel Yeo ◽  
Nico van Zandwijk ◽  
John E. J. Rasko
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Malignant Mesothelioma ◽  
Oncolytic Viruses ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

AbstractMalignant mesothelioma (MM) is a treatment-resistant tumor originating in the mesothelial lining of the pleura or the abdominal cavity with very limited treatment options. More effective therapeutic approaches are urgently needed to improve the poor prognosis of MM patients. Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a novel potential treatment for this incurable solid tumor. The tumor-associated antigen mesothelin (MSLN) is an attractive target for cell therapy in MM, as this antigen is expressed at high levels in the diseased pleura or peritoneum in the majority of MM patients and not (or very modestly) present in healthy tissues. Clinical trials using anti-MSLN CAR T cells in MM have shown that this potential therapeutic is relatively safe. However, efficacy remains modest, likely due to the MM tumor microenvironment (TME), which creates strong immunosuppressive conditions and thus reduces anti-MSLN CAR T cell tumor infiltration, efficacy and persistence. Various approaches to overcome these challenges are reviewed here. They include local (intratumoral) delivery of anti-MSLN CAR T cells, improved CAR design and co-stimulation, and measures to avoid T cell exhaustion. Combination therapies with checkpoint inhibitors as well as oncolytic viruses are also discussed. Preclinical studies have confirmed that increased efficacy of anti-MSLN CAR T cells is within reach and offer hope that this form of cellular immunotherapy may soon improve the prognosis of MM patients.

scholarly journals BCMA in Multiple Myeloma—A Promising Key to Therapy

2021 ◽  
Vol 10 (18) ◽  
pp. 4088
Author(s):  
Martina Kleber ◽  
Ioannis Ntanasis-Stathopoulos ◽  
Evangelos Terpos
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Targeted Treatment ◽  
Treatment Modalities ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.

scholarly journals CAR-T cell therapy – toxicity and its management

2020 ◽  
Vol 51 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Lidia Gil ◽  
Anna Łojko-Dankowska ◽  
Magdalena Matuszak ◽  
Anna Wache ◽  
Adam Nowicki ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Infectious Complications ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T ◽  
New Treatment

AbstractChimeric antigen receptor T-cell (CAR-T) therapy is an effective new treatment for hematologic malignancies. Two anti-CD19 CAR-T products, namely axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B-cell lymphoma after two lines of systemic therapy. Additionally, tisagenlecleucel is indicated for refractory acute lymphoblastic leukemia in pediatric patients and young adults up to 25 years of age. CAR-T cells are undoubtedly a major breakthrough therapy in hematooncology resulting in up to 90% response rate with durable remissions in population with refractory high-risk disease. However, there are serious side effects resulting from CAR-T therapy, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Manifestations of CRS mostly include fever, hypotension, hypoxia, and end organ dysfunction. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasia, seizures, and cerebral edema. Since the symptoms are potentially severe, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. In this article, we present a practical guideline for diagnosis, grading and management of CRS and CAR-T neurotoxicity. In addition, infectious complications and late toxicities including prolonged cytopenias and hypogammaglobulinemia are discussed.

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