Dataset Information

In search of magic bullets: the golden age of immunotherapeutics.

ABSTRACT: Once upon a time, immunology was a black box, inflammatory and autoimmune diseases were a mystery, and relatively blunt tools were used to treat these diseases. In the last 40 years, advances in molecular biology, DNA recombination technology, and genome sequencing allowed immunologists to open the box. As the complexity and diversity of the immune response are unveiled, targeted cellular and molecular therapies now offer rational approaches to treat immune-mediated diseases. Here, we discuss how the tried and true bench-to-bedside strategies resulted in some spectacular successes, along with some puzzling failures. Conversely, the advent of targeted therapies in the clinic has led to a wealth of information that changes how we think about the pathogenesis of immune-mediated diseases and how we categorize disease. In turn, these insights can inform next-generation drug discovery and refine targeted therapies for the appropriate patient subsets.

SUBMITTER: O'Shea JJ

PROVIDER: S-EPMC4200390 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In search of magic bullets: the golden age of immunotherapeutics.

O'Shea John J JJ Kanno Yuka Y Chan Andrew C AC

Cell 20140301 1

Once upon a time, immunology was a black box, inflammatory and autoimmune diseases were a mystery, and relatively blunt tools were used to treat these diseases. In the last 40 years, advances in molecular biology, DNA recombination technology, and genome sequencing allowed immunologists to open the box. As the complexity and diversity of the immune response are unveiled, targeted cellular and molecular therapies now offer rational approaches to treat immune-mediated diseases. Here, we discuss ho ...[more]

PMID: 24679538

Similar Datasets

Project description:Introduction and importanceVulvar penetrating trauma is a rather uncommon occurrence (1). Firearm injuries caused by low-velocity gravitational bullets are a common cause of injuries in war-torn countries such as Somalia [2] (Campbell and Wilbert, 2022). These types of injuries are inflicted on by-standers by wayward bullets. No standard consensus on the appropriate management of vulvar penetrating trauma has been established (3). Here in, we report the successful management of an impacted bullet in the clitoris by a simple incision under local anesthesia. The principles of vulva and clitoris tired bullet trauma management are discussed. In our case, we thought it to be rare and interesting, considering its occurrence.Case presentationIn this report, a 24-year-old woman (gravida 2, para 2) suffered from a vulvar area penetrating bullet injury. Imaging revealed that the foreign body was confined to the clitoris, and no evidence of other parts of the body. Under local anesthesia, the bullet was accessed and removed from the clitoris by performing a minor incision. No complications were observed following the surgical removal of the bullet.Clinical discussionNon-obstetric vulva trauma is an extremely rare occurrence. Typically, the cause of non-obstetric vulvar trauma includes sports-related injuries, straddle injuries, and midline splitting injuries. To the best of our knowledge, this case is unique due to the bullet being retained in the clitoris. The treatment of the foreign body is mostly surgical removal. Under local anesthesia, this patient underwent complete surgical removal of the metallic foreign body. During surgical excision, care should be taken not to damage the urethra and other pelvic issues.ConclusionTo the best of our knowledge, this is the first wayward bullet (not intended for the patient) injury penetrating the vulvar area with a retained bullet in the clitoris. In our case, we thought it to be rare and interesting, considering its occurrence.

Project description:Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners' collaboration. However, no reviews were focused following various preclinical and clinical studies published since the MMV initiation (2000) to till date.We identify promising approaches in the global portfolio of antimalarial medicines, and highlight challenges and patient specific concerns of these novel molecules. We discuss different clinical studies focusing on the evaluation of novel drugs against malaria in different human trials over the past five years.The drugs KAE609 and DDD107498 are still being evaluated in Phase I trials and preclinical developmental studies. Both the safety and efficacy of novel compounds such as KAF156 and DSM265 need to be assessed further, especially for use in pregnant women. Synthetic non-artemisinin ozonides such as OZ277 raised concerns in terms of its insufficient efficacy against high parasitic loads. Aminoquinoline-based scaffolds such as ferroquine are promising but should be combined with good partner drugs for enhanced efficacy. AQ-13 induced electrocardiac events, which led to prolonged QTc intervals. Tafenoquine, the only new anti-relapse scaffold for patients with a glucose-6-phosphate dehydrogenase deficiency, has raised significant concerns due to its hemolytic activity. Other compounds, including methylene blue (potential transmission blocker) and fosmidomycin (DXP reductoisomerase inhibitor), are available but cannot be used in children.At this stage, we are unable to identify a single magic bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.

Dataset Information

In search of magic bullets: the golden age of immunotherapeutics.

Publications

In search of magic bullets: the golden age of immunotherapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets