Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy.

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs. Methods: To improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice. Results: Both ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice. Discussion: These findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.

Increasing access to hematopoietic cell transplantation in Latin America: results of the 2018 LABMT activity survey and trends since 2012.

A total of 5642 hematopoietic cell transplants (HCT) in 5445 patients (2196-40% allogeneic and 3249-60% autologous) were reported by 127 teams in 14 Latin American countries that answered the 2018 LABMT/WBMT Global Transplant Activity survey. The transplant rate (defined as the number of first transplants per 10 million inhabitants per year) was 85 (51 autologous and 34 allogeneic) in 2018. The main indications for allogeneic HCT were acute leukemias (60%), while plasma cell disorders and lymphomas were the most common conditions warranting autologous HCT (50 and 36%, respectively). In the allogeneic HCT, HLA-identical siblings were the main type of donor (44%) followed by related mismatched/haploidentical donors (32%). Peripheral blood stem cells were used in 98% of the autologous and in 64% of the allogeneic transplants. From 2012 to 2018, there was a 64% increase of reported HCT (54% in autologous and 80% in allogeneic). In the allogeneic setting, the most pronounced increase in donor type was observed in haploidentical relatives (from 94 procedures in 2012 up to 710 in 2018), surpassing unrelated donors as of 2017. Significant trends detected in Latin America include rising numbers of the procedures reported, a faster increase in allogeneic HCT compared with autologous HCT and a significant increase in family mismatched/haploidentical donors. The LABMT/WBMT activity survey provides useful data to understand the HCT activity and trends in Latin America.

Acciones para la atención a las particularidades individuales de los estudiantes de Ciencias Médicas: Pinar del Río, 2007 / Efforts to attend to medical students individual issues: Pinar del Río, 2007

En la actualidad en que nuestras universidades están en un momento superior del desarrollo, y donde los retos a enfrentar, por las características de los estudiantes, profesores y escenarios formativos se hacen más complejos, se precisa de establecer acciones con el propósito de contribuir al perfeccionamiento de la atención a las particularidades individuales de los estudiantes a través del proceso docente educativo en la Facultad de Medicina de Pinar del Río y teniendo en cuenta sus individualidades, por sobre todo, dadas las características diversas del ingreso, las posibilidades de aprendizaje y los variados factores que puedan incidir, se propone un sistema de acciones que permita una mejor atención en su preparación, lo que repercutirá favorablemente en los resultados de calidad del proceso y por tanto hablará a favor de su formación integral. Para su elaboración se tuvieron en cuenta los resultados obtenidos en otras investigaciones relacionadas con el tema, el criterio de profesores con elevada experiencia en el trabajo pedagógico en el centro, los fundamentos que aparecen en la literatura consultada y los resultados de encuesta diagnóstica aplicada a 80 estudiantes de primer año de medicina, de una matrícula de 380, que permitió dar fundamento al problema, donde queda determinada la necesidad de estructurar un grupo de acciones planificadas que posibilite realizar de forma más eficiente la atención a los educandos, las que apoyadas en principios psicopedagógicos permitan sugerir la necesaria preparación de todos los que de una forma u otra tengan que ver con este proceso (AU)

A system of actions was proposed to attend to Medical Students individual issues in order to favor their preparation as future comprehensive health professionals and increasing quality of the teaching learning process. Results obtained , pedagogical investigations related to the topic, professors opinions and literature revisions were taken into account to process the information collected. A survey was applied in first academic year of medical studies determining the problems and the needs in order to plan actions which favor the attention to the individual issues in Medical Schools considering psychopedagogical principles and using the available resources efficiently (AU)