Terapias biológicas del cáncer: un enfoque a favor de la accesibilidad / Biological cancer therapies: an approach towards accessibility

RESUMEN Los anticuerpos monoclonales son una poderosa herramienta para el diagnóstico de laboratorio y un instrumento cada vez más utilizado en el tratamiento de diversas enfermedades, siendo uno de los grupos más importantes de drogas en el tratamiento del cáncer. La revolución en el mundo de los anticuerpos ocurre en 1975 cuando Milstein y Köhler desarrollan la técnica de las hibridomas en Cambridge. Objetivo Hacer una revisión del uso de anticuerpos monoclonales en medicina y, en particular, en el tratamiento del cáncer. Se busca aportar una visión generalizada del concepto de anticuerpo monoclonal para explicar su aplicabilidad terapéutica y abordar un enfoque económico y sociosanitario de la obtención y acceso a las nuevas terapias. Método En la caracterización del fenómeno de investigación se empleó el estudio descriptivo, de recolección de datos documental y la correlación entre las distintas fuentes. Discusión Son aún elevados los costos tanto para el paciente como para los sistemas de salud pública, y se ha de optimizar la valoración costo-efectividad de modo que la rentabilidad y el acceso a tiempo para los pacientes puedan ser compatibles. Se deja abierto el reto del desarrollo de nuevos mAbs dirigidos a nuevas dianas, mejorar el perfil de seguridad, evitando o reduciendo las reacciones adversas inmunes y conseguir el abaratamiento del coste de producción mediante mejoras en la biotecnología.(AU)

ABSTRACT Monoclonal antibodies are a useful tool for laboratory diagnosis and an instrument used in the treatment of various diseases and represent one of the most important groups of new drugs for the treatment of cancer. The revolution in the world occured in 1975 when Milstein and Köhler discovered monoclonal antibodies in Cambridge. Objective To review the use of monoclonal antibodies in medicine and in the treatment of cancer. To provide a generalized vision of the concept of monoclonal antibody to explain its therapeutic applicability, and to approach an economic, health-care approach to obtaining and accessing new therapies. Method In the characterization of the research phenomenon, the descriptive study, the collection of documentary data and the correlation between the different sources were used. Discussion However, the costs for both the patient and the public health systems are still high, and the cost-effectiveness assessment must be optimized so that cost-effectiveness and access to time for patients can be compatible. And the challenge of developing new mAbs aimed at new targets, improving the safety profile, avoiding, or reducing adverse immune reactions and achieving lower production costs through improvements in biotechnology, is left open.(AU)

Recent advances in gelatin-based therapeutics.

INTRODUCTION: Biomaterials have provided a wide range of exciting opportunities in tissue engineering and regenerative medicine. Gelatin, a collagen-derived natural biopolymer, has been extensively used in regenerative medicine applications over the years, due to its cell-responsive properties and the capacity to deliver a wide range of biomolecules. AREAS COVERED: The most relevant properties of gelatin as biomaterial are presented together with its main therapeutic applications. The latter includes drug delivery systems, tissue engineering approaches, potential uses as ink for 3D/4D Bioprinting, and its relevance in organ-on-a-chip platforms. EXPERT OPINION: Advances in polymer chemistry, mechanobiology, imaging technologies, and 3D biofabrication techniques have expanded the application of gelatin in multiple biomedical research applications ranging from bone and cartilage tissue engineering, to wound healing and anti-cancer therapy. Here, we highlight the latest advances in gelatin-based approaches within the fields of biomaterial-based drug delivery and tissue engineering together with some of the most relevant challenges and limitations.

Orthobiologics in Pediatric Orthopedics.

Orthobiologics are biologic devices or products used in orthopedic surgery to augment or enhance bone formation. The use of orthobiologics in pediatric orthopedics is less frequent than in other orthopedic subspecialties, mainly due to the naturally abundant healing potential and bone formation in children compared with adults. However, orthobiologics are used in certain situations in pediatric orthopedics, particularly in spine and foot surgery. Other uses have been reported in conjunction with specific procedures involving the tibia and pelvis. The use of bioabsorable implants to stabilize children's fractures is an emerging concept but has limited supporting data.

Orthobiologics in Pediatric Sports Medicine.

Orthobiologics are biological substances that allow injured muscles, tendons, ligaments, and bone to heal more quickly. They are found naturally in the body; at higher concentrations they can aid in the healing process. These substances include autograft bone, allograft bone, demineralized bone matrix, bone morphogenic proteins, growth factors, stem cells, plasma-rich protein, and ceramic grafts. Their use in sports medicine has exploded in efforts to increase graft incorporation, stimulate healing, and get athletes back to sport with problems including anterior cruciate ligament ruptures, tendon ruptures, cartilage injuries, and fractures. This article reviews orthobiologics and their applications in pediatric sports medicine.

Biologic Approaches to Problems of the Hand and Wrist.

Orthobiologics are not used as frequently in the hand and wrist as in other sites. The most frequently reported is the use of bone morphogenetic protein for the treatment of Kienböck disease. Animal studies have described improved tendon healing with the use of platelet-rich plasma (PRP), but no clinical studies have confirmed these results. PRP has been reported to produce improvements in the outcomes of distal radial fractures and osteoarthritis of the trapeziometacarpal in small numbers of patients. The use of orthobiologics in the hand and wrist are promising, but clinical trials are necessary to establish efficacy and safety.

Liposome-Encapsulated Bacteriophages for Enhanced Oral Phage Therapy against Salmonella spp.

Bacteriophages UAB_Phi20, UAB_Phi78, and UAB_Phi87 were encapsulated in liposomes, and their efficacy in reducing Salmonella in poultry was then studied. The encapsulated phages had a mean diameter of 309 to 326 nm and a positive charge between +31.6 and +35.1 mV (pH 6.1). In simulated gastric fluid (pH 2.8), the titer of nonencapsulated phages decreased by 5.7 to 7.8 log units, whereas encapsulated phages were significantly more stable, with losses of 3.7 to 5.4 log units. The liposome coating also improved the retention of bacteriophages in the chicken intestinal tract. When cocktails of the encapsulated and nonencapsulated phages were administered to broilers, after 72 h the encapsulated phages were detected in 38.1% of the animals, whereas the nonencapsulated phages were present in only 9.5%. The difference was significant. In addition, in an in vitro experiment, the cecal contents of broilers promoted the release of the phages from the liposomes. In broilers experimentally infected with Salmonella, the daily administration of the two cocktails for 6 days postinfection conferred similar levels of protection against Salmonella colonization. However, once treatment was stopped, protection by the nonencapsulated phages disappeared, whereas that provided by the encapsulated phages persisted for at least 1 week, showing the enhanced efficacy of the encapsulated phages in protecting poultry against Salmonella over time. The methodology described here allows the liposome encapsulation of phages of different morphologies. The preparations can be stored for at least 3 months at 4°C and could be added to the drinking water and feed of animals.

In vitro hatching of Trichuris suis eggs.

Eggs of the pig whipworm, Trichuris suis ova (TSO), are currently tested in human clinical trials for their potential immunomodulatory capacity. The biological potency of TSO (egg viability and infectivity) is traditionally assessed in Göttingen minipigs as the establishment of intestinal larvae after inoculation with a known number of eggs. To minimize testing in animal models, development of an in vitro egg hatching assay is proposed as a reliable, cost-effective, and a faster alternative to test the egg viability. The present study aimed to investigate the influence of different chemical, physical, and biological factors on egg hatching. Thus, in a series of experiments and in different combinations, the eggs were stimulated with glass beads, artificial gastric juice, bile salt and trypsin solution, fermentation gut medium, or stimulated with mucosal scrapings from the ileum and the large intestine of the infected and uninfected Göttingen minipig. Mechanical stimulation with glass beads presented a simple and reproducible method for egg hatching. However, incubation of eggs with mucosal scrapings from the ileum, caecum, and colon for 24 h at 38 °C significantly increased hatching.

Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials.

Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.

Manufacturing and device options for the delivery of biotherapeutics.

Biotherapeutic aerosol formulations are an intense area of interest for systemic and local drug delivery. This article provides a short overview of typical factors required specifically for biotherapeutic aerosol formulation design, the processing options open for consideration, and the issue of inhalation device selection. Focusing on spray drying, four case studies are used to highlight the relevant issues, describing investigations into: (1) the mechanical stresses occurring in bacteriophage formulations during spray-dryer atomization; (2) modeling of the spray-dryer process and droplet drying kinetics, to assist process design and predictions of formulation stability; (3) a predictive approach to the design and processing of a five-component dry powder aerosol formulation; and (4) the survival of bacteriophages after pressurized metered dose inhaler atomization.