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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 -
The American Journal of Dermatopathology Jun 2024Cutaneous ciliated cysts are rare benign lesions most commonly seen in the lower extremities of young female patients. There is still ongoing debate about the origin of...
Cutaneous ciliated cysts are rare benign lesions most commonly seen in the lower extremities of young female patients. There is still ongoing debate about the origin of these cysts, with the most common theories being Mullerian heterotopia and eccrine gland metaplasia. To further increase the data pool, we present 2 new cutaneous ciliated cyst cases and gathered data about all 67 cases of literature. We want to highlight that immunohistochemistry and demographic information may play a key role in distinguishing between the 2 possible origins of this cyst, namely estrogen receptor, progesterone receptor, and carcinoembryonic antigen immunohistochemistry. Estrogen receptor and progesterone receptor nuclear positivity is proof of Mullerian origin, but when they are negative with a positive carcinoembryonic antigen, the most likely origin is eccrine gland metaplasia. We advocate using the terms "Cutaneous Mullerian Cyst" and "Ciliated Cutaneous Eccrine Cyst" instead of "Cutaneous Ciliated Cyst" to accurately indicate their distinct origins.
PubMed: 38941541
DOI: 10.1097/DAD.0000000000002777 -
ACS Chemical Biology Jun 2024Chemokines are an important family of small proteins integral to leukocyte recruitment during inflammation. Dysregulation of the chemokine-chemokine receptor axis is...
Chemokines are an important family of small proteins integral to leukocyte recruitment during inflammation. Dysregulation of the chemokine-chemokine receptor axis is implicated in many diseases, and both chemokines and their cognate receptors have been the targets of therapeutic development. Analysis of the antigen-binding regions of chemokine-binding nanobodies revealed a sequence motif suggestive of tyrosine sulfation. Given the well-established importance of post-translational tyrosine sulfation of receptors for chemokine affinity, it was hypothesized that the sulfation of these nanobodies may contribute to chemokine binding and selectivity. Four nanobodies (16C1, 9F1, 11B1, and 11F2) were expressed using amber codon suppression to incorporate tyrosine sulfation. The sulfated variant of 16C1 demonstrated significantly improved chemokine binding compared to the non-sulfated counterpart, while the other nanobodies displayed equipotent or reduced affinity upon sulfation. The ability of tyrosine sulfation to modulate chemokine binding, both positively and negatively, could be leveraged for chemokine-targeted sulfo-nanobody therapeutics in the future.
PubMed: 38941516
DOI: 10.1021/acschembio.4c00230