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Cancer Genomics & Proteomics 2024Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor...
BACKGROUND/AIM
Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations.
MATERIALS AND METHODS
Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells.
RESULTS
JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay.
CONCLUSION
Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.
Topics: Humans; Female; Ovarian Neoplasms; Transcription Factors; DNA-Binding Proteins; Adenocarcinoma, Clear Cell; T-Lymphocytes, Cytotoxic; Cell Line, Tumor; Antigens, Neoplasm; HLA-A2 Antigen; Membrane Proteins
PubMed: 38944423
DOI: 10.21873/cgp.20460 -
Transplantation and Cellular Therapy Jun 2024Center for International Blood and Marrow Transplant Research (CIBMTR) prepares an annual set of summary slides to detail the trends in transplantation and cellular...
BACKGROUND
Center for International Blood and Marrow Transplant Research (CIBMTR) prepares an annual set of summary slides to detail the trends in transplantation and cellular therapies. For the first time in the 2023 summary slides, CIBMTR incorporates data for patients receiving chimeric antigen receptor T-cell (CAR-T) infusions. In addition, the data on patient-reported outcomes (PROs) is also included.
OBJECTIVES
This report aims to update the annual trends in US HCT activity and incorporate data on the use of CAR-T therapies. Here we also aim to present and describe the development, implementation, and current status of the PRO data collection.
STUDY DESIGN
In August 2020, CIBMTR launched the Protocol for Collection of Patient Reported Outcomes Data (CIBMTR PRO Protocol). The CIBMTR PRO Protocol operates under a centralized infrastructure to reduce burden to centers. Specifically, PRO data is collected from a prospective convenience sample of adult HCT and CAR-T patients who received treatment at contributing centers and consented for research. Data are merged and stored with the clinical data and used under the governance of the CIBMTR Research Database Protocol. Participants answer a series of surveys developed by the Patient Reported Outcomes Measurement Information System© (PROMIS) focusing on physical, social and emotional, and others measures assessing financial well-being, occupational functioning, and social determinants of health. To complement traditionally measured clinical outcomes, the surveys are administered at the same timepoints that clinical data is routinely collected.
RESULTS
As of September 2023, PRO data from 993 patients across 25 different centers has been collected. With the goal of incorporating these important patient perspectives into standard clinical care, CIBMTR has added the PRO data to Data Back to Centers (DBtC). Through expanding the data types represented in the registry, CIBMTR aims to support holistic research accounting for the patient perspective in improving patient outcomes.
CONCLUSION
PRO data at CIBMTR aims to provide the foundation for future large scale, population-level evaluations to determine areas for improvement, emerging disparities in access and health outcomes (eg, by age, race, and ethnicity), and new therapies that may impact current treatment guidelines. Continuing to collect and grow the PRO data is critical for understanding these changes and identifying methods for improving patient quality of life.
PubMed: 38944153
DOI: 10.1016/j.jtct.2024.06.021 -
Expert Opinion on Biological Therapy Jun 2024CAR T cells have generated great excitement due to their remarkable clinical response rates in selected hematologic malignancies. However, these engineered immune cells... (Review)
Review
INTRODUCTION
CAR T cells have generated great excitement due to their remarkable clinical response rates in selected hematologic malignancies. However, these engineered immune cells are living drugs which are hard to control after administration.
AREAS COVERED
We discuss small molecule-regulated switch systems which can potentially be used to control CAR T cell function within the patient, as well as the most important obstacles in the CAR T cell field, which might be overcome with those switch systems.
EXPERT OPINION
There is an urgent need to develop advanced switch systems. Once available, we expect that they will open up new avenues for future CAR T cell generations.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Animals; Hematologic Neoplasms
PubMed: 38943466
DOI: 10.1080/14712598.2024.2371034 -
American Journal of Hematology Jun 2024Multiple myeloma accounts for approximately 10% of hematologic malignancies.
DISEASE OVERVIEW
Multiple myeloma accounts for approximately 10% of hematologic malignancies.
DIAGNOSIS
The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L and urine monoclonal protein is ≥200 mg/24 h), or >1 focal lesion on magnetic resonance imaging.
RISK STRATIFICATION
The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma.
RISK-ADAPTED INITIAL THERAPY
In patients who are candidates for autologous stem cell transplantation, induction therapy consists of anti-CD38 monoclonal antibody plus bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT). Selected standard risk patients can delay transplant until first relapse. Frail patients who not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression.
MAINTENANCE THERAPY
Standard risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma.
MANAGEMENT OF RELAPSED DISEASE
A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse. Chimeric antigen receptor T (CAR-T) cell therapy and bispecific antibodies are additional options.
PubMed: 38943315
DOI: 10.1002/ajh.27422 -
Journal of Nanobiotechnology Jun 2024Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and... (Review)
Review
Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.
Topics: Nanoparticles; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Animals; Lipids; T-Lymphocytes; Neoplasms; Liposomes
PubMed: 38943167
DOI: 10.1186/s12951-024-02630-1 -
Korean Journal of Radiology Jul 2024This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the... (Meta-Analysis)
Meta-Analysis Review
This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the correlation of apparent diffusion coefficient (ADC) with hormone receptor status and prognostic biomarkers. Our meta-analysis includes data from 52 studies examining ADC values in relation to estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status. The results indicated significant differences in ADC values among different receptor statuses, with ER-positive, PgR-positive, HER2-negative, and Ki-67-positive tumors having lower ADC values compared to their negative counterparts. This study also highlights the potential of advanced DWI techniques such as intravoxel incoherent motion and non-Gaussian DWI to provide additional insights beyond ADC. Despite these promising findings, the high heterogeneity among the studies underscores the need for standardized DWI protocols to improve their clinical utility in breast cancer management.
Topics: Humans; Breast Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Biomarkers, Tumor; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Ki-67 Antigen
PubMed: 38942456
DOI: 10.3348/kjr.2023.1188 -
Critical Reviews in Oncology/hematology Jun 2024In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The... (Review)
Review
In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The emergence of Chimeric Antigen Receptor T-cell (CAR-T) therapy has marked a pivotal shift in the therapeutic landscape, offering novel avenues for the management of MM, particularly for those with relapsed or refractory disease. This innovative treatment modality not only targets malignant cells with precision but also influences the bone microenvironment, presenting both challenges and opportunities in patient care. In this comprehensive review, we aim to examine the multifaceted aspects of bone disease in patients with multiple myeloma and concurrent CAR-T therapy, highlighting its clinical ramifications and the latest advancements in diagnostic modalities and therapeutic interventions. The article aims to synthesize current understanding of the interplay between myeloma cells, CAR-T cells, and the bone microenvironment in the context of current treatment strategies in this challenging and unique patient population.
PubMed: 38942219
DOI: 10.1016/j.critrevonc.2024.104429 -
Biomedicine & Pharmacotherapy =... Jun 2024Over the last decade, discovery of novel therapeutic method has been attention by the researchers and has changed the therapeutic perspective of hematological... (Review)
Review
Over the last decade, discovery of novel therapeutic method has been attention by the researchers and has changed the therapeutic perspective of hematological malignancies. Although NK cell play a pivotal role in the elimination of abnormal and cancerous cells, there are evidence that NK cell are disarm in hematological malignancy. Chimeric antigen receptor NK (CAR-NK) cell therapy, which includes the engineering of NK cells to detect tumor-specific antigens and, as a result, clear of cancerous cells, has created various clinical advantage for several human malignancies treatment. In the current review, we summarized NK cell dysfunction and CAR-NK cell based immunotherapy to treat AML patient.
PubMed: 38941897
DOI: 10.1016/j.biopha.2024.117024 -
International Immunopharmacology Jun 2024T cells suffer from long-term antigen stimulation and insufficient energy supply, leading to a decline in their effector functions, memory capabilities, and... (Review)
Review
T cells suffer from long-term antigen stimulation and insufficient energy supply, leading to a decline in their effector functions, memory capabilities, and proliferative capacity, ultimately resulting in T cell exhaustion and an inability to perform normal immune functions in the tumor microenvironment. Therefore, exploring how to restore these exhausted T cells to a state with effector functions is of great significance. Exhausted T cells exhibit a spectrum of molecular alterations, such as heightened expression of inhibitory receptors, shifts in transcription factor profiles, and modifications across epigenetic, metabolic, and transcriptional landscapes. This review provides a comprehensive overview of various strategies to reverse T cell exhaustion, including immune checkpoint blockade, and explores the potential synergistic effects of combining multiple approaches to reverse T cell exhaustion. It offers new insights and methods for achieving more durable and effective reversal of T cell exhaustion.
PubMed: 38941674
DOI: 10.1016/j.intimp.2024.112571 -
Annual Review of Immunology Jun 2024Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses... (Review)
Review
Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.
Topics: Humans; Poxviridae; Immune Evasion; Animals; Poxviridae Infections; Cytokines; Signal Transduction; Viral Proteins; Antigen Presentation; Host-Pathogen Interactions
PubMed: 38941604
DOI: 10.1146/annurev-immunol-090222-110227