TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis

We have assessed the efficacy and safety of Escherichia coli extract (ECE; Uro-Vaxom(R)) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2+/-5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis.

Efecto in vitro del extracto bacteriano de S. aureus en la quimiocinesis y quimiotaxis de células polimorfonucleares / Effect the extract of Staphylococcus aureus in vitro can modify chemokinesis and induce chemotaxis of polimorphonuclear cells

El propósito del trabajo fue determinar si el extracto de Staphylococcus aureus in vitro puede modificar la quimiocinesis e inducir la quimiotaxis de las células polimorfonucleares de la sangre periférica en donadores sanos. Se determinó la quimiocinesis y la quimiotaxis de los polimorfonucleares de la sangre periférica de 30 donadores sanos de uno y otro sexo con un límite de edad entre 18 y 40 años. Se les extrajeron 5 mL de sangre periférica separando los polimorfonucleares por el método de Boyum y se retaron con extracto de Staphylococcus aureus y C5a como quimiotácticos, y solución de Hank para medir quimiocinesis. Esta tuvo un promedio de 54.6ñ8.8 µm, la respuesta quimiotáctica a C5a fue 89ñ12.5 µm y con el extracto bacteriano fue 103ñ20.1 µm (p<0.001. Análisis estadístico: prueba de Wilcoxon. Se concluye que el extracto completo de Staphylococcus aureus estímula in vitro la quimiotaxis de polimorfonucleares de donadores sanos y que esta estimulación es comparable con lo quimioatrayentes conocidos como C5a

Solubilización de la membrana de espermatozoide humano con n-dodecil sarcosinato de sodio: II. Estudios sobre el extracto / Spermatozoa submitted to ionic detergent treatment: studen on the sodium n-dodceyl sarcosinate extract

El n-dodecil sarcosinato de sodio produce la solubilización del espermatozoide humano con algo de contaminación acrosomal. El extracto está compuesto por una mezcla de productos con pesos moleculares y características inmunológicas similares a las del plasma seminal humano. El hecho de que la antigenicidad se mantenga luego de la solubilización, hace que ésta sea un comienzo útil en el aislamiento de moléculas que juegan un papel en la infertilidad por causas inmunológicas

Acción del extracto leucocitario dializado sobre la maduración de timocitos in vitro / Action of dialyzed leukocyte extract on in vitro maturation of thymocytes

Basado en las sugerencias tempranas de Lawrence, acerca de que los efectos inmunológicos específicos y no específicos del extracto leucocitario dializado (ELD) puedan derivar de su capacidad de iniciar la maduración de una célula primitiva de la serie T, se estudiaron los efectos del ELD sobre la adquisición de la capacidad de respuesta blastogénica de los timocitos de ratón a los fitomitógenos: PHA, con A y PWM y sobre la conversión de los timocitos hidrocortisona-sensibles en hidrocortisona-resistentes como indicadores reconocidos de la maduración de células T. Nuestros resultados destacan el ELD como posible inductor de la maduración y diferenciación terminal de las células tímicas, propiedad exclusiva del ELD respecto a otros inmunosupresores y fuente de importantes implicaciones terapéuticas