Improving and Maintaining Responses in Pediatric B–Cell Acute Lymphoblastic Leukemia Chimeric Antigen Receptor–T Cell Therapy
Chimeric antigen receptor T therapy has heralded a new era in the treatment of acute lymphoblastic leukemia (ALL) and other hematologic malignancies. In this autologous immunotherapy, patient-derived T cells are genetically engineered and then infused back to kill the leukemia cells. The observed response rates in ALL are a testament to the success of this therapy. However, there have been instances where the patients either did not respond or relapsed after initial response. Emergence of resistance due to antigen loss and T-cell exhaustion has been observed. This poses a challenge in making this therapy successful for eve...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Challenges and Solutions to Bringing Chimeric Antigen Receptor T-Cell Therapy to Myeloid Malignancies
Myeloid malignancies including myelodysplastic syndromes and acute myeloid leukemia are a group of clonal hematopoietic stem progenitor cell disorders mainly effecting the elderly. Chemotherapeutic approaches improved the outcome in majority of the patients, but it is generally associated with severe toxicities and relapse and does not benefit all the patients. With the success of adoptive cell therapies including chimeric antigen receptor T-cell therapy in treating certain B-cell malignancies, these therapeutic approaches are also being tested for myeloid malignancies, but the preclinical and limited clinical trial data s...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
How Do We Meet the Challenge of Chimeric Antigen Receptor T-Cell Therapy for Solid Tumors?
Immune checkpoint inhibition has vastly improved the treatment of solid tumors, but most patients do not experience durable clinical benefit, so novel immunotherapeutic approaches are needed. Autologous T cells genetically engineered to express chimeric antigen receptors (CARs) have led to unprecedented clinical success in hematologic malignancies, and increasing efforts are actively being pursued to translate these benefits to the solid tumor arena. However, solid tumors present unique challenges for CAR T-cell development. In this review, we examine the potential barriers to progress and present emerging approaches to ov...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Neurotoxicity Biology and Management
Chimeric antigen receptor (CAR) T-cell therapy is a highly effective new treatment for relapsed and refractory hematological cancers but is associated with the novel treatment-limiting toxicities of cytokine release syndrome and neurotoxicity. Neurotoxicity, now more commonly referred to as immune effector cell–associated neurotoxicity syndrome (ICANS), is a clinical and neuropsychiatric syndrome that can occur in the days to weeks following CAR T-cell and other T-cell–engaging therapies. While the clinical characteristics of ICANS have been well described, its pathophysiology is poorly understood, and best treatment a...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Cytokine Release Syndrome Biology and Management
The successful application of chimeric antigen receptor (CAR) T cells for the treatment of relapsed and refractory B-cell malignancies has ushered in a new frontier for the immunotherapy of cancer. Despite its successes, CAR T-cell therapy presents several challenges. Cytokine release syndrome (CRS) triggered by robust and exponential CAR T-cell expansion is the most common adverse effect and may be severe or life-threatening. Although modulation of the interleukin 6 axis was appreciated early on as a means to manage CRS, the exact underlying mechanisms leading to severe CRS remain to be elucidated. What is clear is that s...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Chimeric Antigen Receptor T Cells for Multiple Myeloma: The Journey So Far—And the Road Ahead
Despite improvements in effective therapy, multiple myeloma remains incurable, and virtually all patients will face relapsed disease at some point after diagnosis. The prognosis for relapsed myeloma after developing resistance to anti-CD38 monoclonal antibodies, proteasome inhibitors, immunomodulatory agents, and autologous stem cell transplantation has been poor; however, the development of immune effector cell therapy with chimeric antigen receptor (CAR) T cells may dramatically improve the outlook for patients, although none of these therapies are approved for MM to date. Herein, we review the development and history of...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Chimeric Antigen Receptor T Cells for B-Cell Lymphoma
Anti-CD19–directed chimeric antigen receptor (CAR) T-cell therapy yields durable remissions in up to 40% of patients with chemoresistant aggressive B-cell non-Hodgkin lymphoma (NHL), a group of patients expected only to survive on average 6 months. Although longer follow-up is needed to define durability, CD19 CAR T cells are demonstrating similar promise in other B-NHL subtypes such as mantle cell lymphoma and the indolent B-cell NHLs. This transformative therapy, however, remains hamstrung by its associated toxicities of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, as well as ...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Chimeric Antigen Receptor T-Cell Therapy for B-Cell Acute Lymphoblastic Leukemia: Current Landscape in 2021
Immunotherapy with T cells engineered to express a chimeric antigen receptor (CAR T cells) is reshaping the management of patients with relapsed or refractory B-cell malignancies. High efficacy of CD19-targeted CAR T cells has been reported in children and adults with B-cell acute lymphoblastic leukemia (B-ALL), with complete responses without detectable minimal residual disease occurring in approximately 80% to 90% of patients. This led to the approval of tisagenlecleucel (Kymriah) by the Food and Drug Administration based on the results of the ELIANA trial. Although CD19 CAR T-cell therapy may be curative in children, re...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Chimeric Antigen Receptor Design Today and Tomorrow
The US Food and Drug Administration has approved 3 chimeric antigen receptor (CAR) T-cell therapies. For continued breakthroughs, novel CAR designs are needed. This includes different antigen-binding domains such as antigen-ligand binding partners and variable lymphocyte receptors. Another recent advancement in CAR design is Boolean logic gates that can minimize on-target, off-tumor toxicities. Recent studies on the optimization of costimulatory signaling have also shown how CAR design can impact function. By using specific signaling pathways and transcription factors, CARs can impact T-cell gene expression to enhance func...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Chimeric Antigen Receptor–Modified Immune Effector Cell Therapies: Learning From the Present; Charting a Path to the Future
No abstract available (Source: The Cancer Journal)
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Introduction from Guest Editor Source Type: research
Coping Strategies and Their Impact on Emotional Distress and Fatigue Among Breast Cancer Survivors: A Cross-sectional Survey
This study examined the relations between subjective stress and strategies for coping with stress (emotion control strategies and self-compassion), as well as the relations between emotional distress and fatigue.
Methods
The study used a cross-sectional survey design. Participants were 170 women aged 24 to 82 years with diagnoses of breast cancer stages I to III who were 1 to 12 months postchemotherapy, with no current evidence of disease and no previous cancer diagnosis. Participants were recruited by consecutive sampling, and the overall response rate was 85%.
Results
Higher subjective stress was associated...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Original Article Source Type: research
“Triple-Negative Breast Cancer Central Nervous System Metastases From the Laboratory to the Clinic”
Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers and has an incidence as high as 50% of brain metastases once patients develop advanced disease. The lack of targeted and effective therapies, characteristic of this subtype of breast cancer, is especially evident once central nervous system (CNS) metastases occur. Compared with other subtypes of breast cancer, TNBC patients have the shorter interval from diagnosis to development of brain metastases and the shorter overall survival once they occur, a median of 4 to 6 months. Preclinical studies of TNBC and CNS microenvironment are actively ongoin...
Source: The Cancer Journal - January 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
PARP Inhibitors in Triple-Negative Breast Cancer Including Those With BRCA Mutations
Poly(ADP-ribose) polymerase (PARP) is involved in single-strand DNA break base excision repair. PARP inhibition causes synthetic lethality in breast cancers associated with germline BRCA1 and BRCA2 mutations and is routinely used in clinical practice for metastatic breast cancer. Breast cancers with homologous recombination deficiency or BRCAness, most commonly triple-negative breast cancers, may also benefit. Currently, PARP inhibitor use for triple-negative breast cancer with wild-type BRCA does not have definitive efficacy; however, this is an area of active research. Further clinical and translational data may identify...
Source: The Cancer Journal - January 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Immunotherapy in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is an aggressive subtype of mammary carcinoma. A subset of TNBC is immune activated, suggesting that immunotherapy may be a viable treatment strategy. Phase III clinical trials have shown that atezolizumab or pembrolizumab is well-tolerated in combination with chemotherapy, with progression-free survival benefit in metastatic programmed death ligand-1 (PD-L1)–positive TNBC patients treated first line. Based on IMpassion130, the combination of atezolizumab and nab-paclitaxel is now considered a standard of care for the treatment of PD-L1–positive advanced TNBC. In early TNBC, pembrol...
Source: The Cancer Journal - January 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Targeted Treatment of Triple-Negative Breast Cancer
Triple-negative breast cancer is increasingly recognized as a heterogeneous entity that can be categorized according to histologic, molecular, and clinical subtypes. While chemotherapy remains the backbone of treatment for this disease, there are now several available targeted agents including immunotherapy, poly(adenosine diphosphate-ribose) polymerase inhibitors, and most recently a Food and Drug Administration–approved antibody-drug conjugate sacituzumab govitecan-hziy as a third-line treatment of metastatic triple-negative breast cancer. We review several actionable targets for triple-negative breast cancer and descr...
Source: The Cancer Journal - January 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research
