Development of Cell and Gene Therapies for Clinical Use in the US and EU: Summary of Regulatory Guidelines.

Recent decades have seen advancements in the management and treatment of difficultto- treat diseases such as cancer. A special class of therapeutics called cell and gene therapy has been introduced in the past 10 years. Cell and gene therapy products have strengthened the treatment options for life-threatening diseases with unmet clinical needs and also provided the possibility of a potential cure for the disease in some of the patients.

Optimizing outcomes and managing adverse events in locally advanced or metastatic urothelial cancer: a clinical pharmacology perspective.

Introduction: Bladder cancer (BC) is the sixth most common type of cancer with epithelial/urothelial and non-urothelial origins. Urothelial carcinoma (UC) involves neoplastic cells of epithelial origin and accounts for 90% of all BC cases. Current review aims to discuss the latest advances and challenges in the treatment of UC with an emphasis on clinical pharmacology considerations.

Dose fractionation of CAR-T cells. A systematic review of clinical outcomes.

CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy.

Dose-response correlation for CAR-T cells: a systematic review of clinical studies.

The potential of chimeric antigen receptor (CAR) T cells to successfully treat hematological cancers is widely recognized. Multiple CAR-T cell therapies are currently under clinical development, with most in early stage, during which dose selection is a key goal. The objective of this review is to address the question of dose-dependent effects on response and/or toxicity from available CAR-T cell clinical trial data.

Concept of the Number Needed to Treat for the Analysis of Pain Relief Outcomes in Patients Treated with Spinal Cord Stimulation.

In the rapidly evolving field of spinal cord stimulation (SCS), measures of treatment effects are needed to help understand the benefits of new therapies. The present article elaborates the number needed to treat (NNT) concept and applies it to the SCS field. We reviewed the basic theory of the NNT, its calculation method, and its application to historical controlled trials of SCS.

Safety and Efficacy of 10 kHz Spinal Cord Stimulation for the Treatment of Refractory Chronic Migraine: A Prospective Long-Term Open-Label Study.

Background: Refractory chronic migraine (rCM) is a highly disabling condition for which novel safe and effective treatments are needed. Safety and long-term efficacy of paresthesia-free high cervical 10 kHz spinal cord stimulation (SCS) were here prospectively evaluated for the treatment of rCM.

Materials And Methods: Twenty adults with rCM (mean numbers of preventive treatments failed: 12.

Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations.

The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the development of combination therapies with anti-PD-1/PD-L1 blockers as a backbone. As more and more drugs with translational potential are identified, the number of clinical trials evaluating combinations has increased considerably and the demand to prioritize combinations having potential for success over the ones that are unlikely to be successful is rising. This review aims to address the unmet need to prioritize cancer immunotherapy combinations through comprehensive search of potential drugs and ranking them based on their mechanism of action, clinical efficacy and safety.

Targeting TIGIT for Immunotherapy of Cancer: Update on Clinical Development.

Immune checkpoint blockers have dramatically improved the chances of survival in patients with metastatic cancer, but only a subset of the patients respond to treatment. Search for novel targets that can improve the responder rates and overcome the limitations of adverse events commonly seen with combination therapies, like PD-1 plus CTLA-4 blockade and PD-1/PD-L1 plus chemotherapy, led to the development of monoclonal antibodies blocking T-cell immunoglobulin and ITIM domain (TIGIT), a inhibitory checkpoint receptor expressed on activated T cells and NK cells. The strategy showed potential in pre-clinical and early clinical studies, and 5 molecules are now in advanced stages of evaluation (phase II and above).

Decreased Opioid Consumption and Durable Pain Relief in Patients Treated with 10 kHz SCS: A Retrospective Analysis of Outcomes from Single-Center.

Background: Chronic pain is frequently treated with opioid analgesics, but there is limited evidence for efficacy for chronic use of opioids and the drugs pose significant risks to patients' physical and mental health. Spinal cord stimulation delivered at a frequency of 10,000 Hertz (10 kHz SCS) is a minimally invasive therapy with demonstrated efficacy and safety in treating chronic pain that has also been associated with decreased opioid use.

Objective: To evaluate opioid reduction and pain relief in real-world cohort.

High-frequency (10 kHz) spinal cord stimulation for the treatment of focal, chronic postsurgical neuropathic pain: results from a prospective study in Belgium.

Chronic postsurgical pain (CPSP) is a common complication of surgery. This study was conducted to evaluate the efficacy and safety of paresthesia-free, 10-kHz spinal cord stimulation (SCS) as a treatment for CPSP. Subjects in this prospective, single-arm study had an average pain intensity of ≥5 cm on a 10-cm visual analog scale.

Efficacy and Safety of 10 kHz Spinal Cord Stimulation Using Cervical and Thoracic Leads: A Single-Center Retrospective Experience.

Introduction: Spinal cord stimulation (SCS) with lower thoracic leads has been studied extensively. However, the evidence base for cervical SCS is less well developed, and reports of multiarea SCS lead placement are uncommon. Therefore, this single-center retrospective study evaluated outcomes from 10-kHz SCS with cervical or combined cervical and thoracic lead placement.

Pain Relief and Safety Outcomes with Cervical 10 kHz Spinal Cord Stimulation: Systematic Literature Review and Meta-analysis.

Background: Chronic pain in head, neck, shoulders and upper limbs is debilitating, and patients usually rely on pain medications or surgery to manage their symptoms. However, given the current opioid epidemic, non-pharmacological interventions that reduce pain, such as spinal cord stimulation (SCS), are needed. The purpose of this study was to review the evidence on paresthesia-free 10 kHz SCS therapy for neck and upper extremity pain.

Amelioration of lower limb pain and foot drop with 10 kHz spinal cord stimulation: A case series.

There are limited treatment options for patients with foot drop and associated lower back and/or leg pain. We present a case series of three patients who received permanent implantation of 10 kHz spinal cord stimulation (10 kHz SCS) devices. Following treatment, all patients reported sustained improvements in lower back and leg pain, foot mechanics and function which resulted in increased mobility and cessation of opioid use for pain management.

A Retrospective Review of Lead Migration Rate in Patients Permanently Implanted with Percutaneous Leads and a 10 kHz SCS Device.

Background: Spinal cord stimulation (SCS) has been used over decades for pain management, but migration of percutaneous leads has been the most common complication. Better surgical techniques and newer SCS technologies likely reduced the incidence of lead migration requiring surgical revision, although data are sparse. This study aimed to retrospectively evaluate the incidence of clinically significant percutaneous lead migration in patients permanently implanted with a 10 kHz SCS system.

10 kHz Spinal Cord Stimulation for the Treatment of Failed Back Surgery Syndrome with Predominant Leg Pain: Results from a Prospective Study in Patients from the Dutch Healthcare System.

Introduction: Persistent back/and or leg pain is a common outcome after spinal surgery (otherwise known as failed back surgery syndrome [FBSS]). Studies have shown that spinal cord stimulation (SCS) at 10 kHz provides effective analgesia in FBSS patients with both back and leg pain symptoms and in those with predominant back pain. This study is the first to evaluate the therapy in FBSS patients with predominant leg pain.

Ten kilohertz SCS for Treatment of Chronic Upper Extremity Pain (UEP): Results from Prospective Observational Study.

Background: Chronic upper extremity pain (UEP) has complex etiologies and is often disabling. It has been shown that 10 kHz SCS can provide paresthesia-free and durable pain relief in multiple pain types and improve the quality of life of patients.

Objective: To gain additional evidence on the safety and effectiveness of 10 kHz SCS for the treatment of chronic UEP.

Pain relief and opioid usage in upper limb and neck pain patients after 10-kHz spinal cord stimulation treatment: subanalysis of USA studies.

It is argued that chronic pain patients who reduce/eliminate their opioids may have compromised pain relief. This study therefore aimed to analyze if reduced opioid consumption associated with 10-kHz spinal cord stimulation adversely affected pain relief. analysis was performed on data from two prospective studies in subjects with upper limbs and neck pain conducted in USA.

Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities.

Tremendous innovation is underway among a rapidly expanding repertoire of promising personalized immune-based treatments. Therapeutic cancer vaccines (TCVs) are attractive systemic immunotherapies that activate and expand antigen-specific CD8 and CD4 T cells to enhance anti-tumor immunity. Our review highlights key issues impacting TCVs in clinical practice and reports on progress in development.

10-kHz spinal cord stimulation treatment for painful diabetic neuropathy: results from analysis of the SENZA-PPN study.

Previous studies of 10 kHz spinal cord stimulation demonstrated its safety and efficacy for treatment of neuropathic pain of the trunk and/or limbs. This study analyzed data from a subset of subjects with painful diabetic neuropathy enrolled in a prospective, multicenter study of peripheral polyneuropathy with various etiologies. Of the eight subjects that had permanent devices, seven attended the 12-month follow-up assessment.

A Prospective, Multi-Center, Clinical Trial of a 10-kHz Spinal Cord Stimulation System in the Treatment of Chronic Pelvic Pain.

Background: Chronic pelvic pain (CPP) is a debilitating condition that often leads to disability and does not respond to conventional treatments. This study was conducted to evaluate the effects of paresthesia-independent 10-kHz spinal cord stimulation (SCS) in subjects with CPP.

Methods: This prospective, single-arm pilot study enrolled subjects with clinical diagnoses of CPP and mean pain scores of ≥ 5.

Retrospective Analysis of Real-World Outcomes of 10 kHz SCS in Patients with Upper Limb and Neck Pain.

Background: Patients living with chronic upper limb and neck (ULN) pain are reliant on often ineffective therapies as they face limited options for effective long-term treatment.

Objective: Prospective clinical studies have demonstrated that high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS) is effective in treating chronic pain in multiple etiologies including ULN pain. This study aimed at validating the findings from clinical studies on ULN in a real-world cohort.

Treatment of Chronic Abdominal Pain With 10-kHz Spinal Cord Stimulation: Safety and Efficacy Results From a 12-Month Prospective, Multicenter, Feasibility Study.

Introduction: Chronic abdominal pain (CAP) can arise from multiple conditions, including inflammatory disorders, trauma because of injury or surgery, or structural or functional causes. This prospective, single-arm study was designed to evaluate the safety and efficacy of 10-kHz spinal cord stimulation (SCS) in patients with intractable CAP over a 12-month follow-up period.

Methods: Subjects with CAP who had been refractory to conventional medical treatment for at least 3 months resulting in self-reported pain scores of ≥5 cm on a 10-cm visual analog scale were enrolled at 4 centers in the United States.

Nuclear localization of ING3 is required to suppress melanoma cell migration, invasion and angiogenesis.

Inhibitor of growth family member 3 (ING3), a tumor suppressor, plays crucial roles in cell cycle regulation, apoptosis and transcription. Previous studies suggest important roles of nuclear ING3, however, the nuclear localization sequence (NLS) of ING3 is not defined and its biological functions remain to be elucidated. In this study, various ING3 mutants were generated to identify its NLS.