P3 mAb: An Immunogenic Anti-NeuGcGM3 Antibody with Unusual Immunoregulatory Properties.

P3 is a murine IgM mAb that recognize N-glycosylated gangliosides, sulfatides, and antigens expressed in melanoma, breast, and lung human tumors. This antibody has the ability to trigger an IgG antibody response in the syngeneic BALB/c model, even when it is administered in the absence of adjuvant or carrier protein. The mechanism by which the P3 mAb, a self-immunoglobulin, induce this immune response in the absence of co-stimulatory or classical danger signals is still unknown. In the present paper we show that the high immunogenicity of P3 mAb depends not only on CD4 but also on CD8(+) T cells, since the depletion of CD8(+) or CD4(+) T cells led to the loss of P3 mAb immunogenicity in the syngeneic model. Furthermore, the immunization with P3 mAb enhanced the recovery of the CD8(+) T cell population in mice treated with an anti-CD8a antibody. Additionally, the immunization with P3 mAb restored the capacity of immunosuppressed mice to reject allogeneic tumors, a mechanism mediated by the action of CD8(+) T cells. Finally, in mice with cyclophosphamide induced lymphopenia, the administration of P3 mAb accelerated the recovery of both CD4(+) and CD8(+) T cells. These results show new possibilities for B and CD8(+) T cells interactions during the immune response elicited by a self-protein. Furthermore they point to P3 mAb as a potential interesting candidate for the treatment of immunosuppressed patients.

Anti-NeuGcGM3 antibodies, actively elicited by idiotypic vaccination in nonsmall cell lung cancer patients, induce tumor cell death by an oncosis-like mechanism.

1E10 is a murine anti-idiotypic mAb specific for an idiotypic mAb that reacts with NeuGc-containing gangliosides, sulfatides, and Ags expressed in some human tumors. In melanoma, breast, and lung cancer patients, this anti-idiotypic Ab was able to induce a specific Ab response against N-glycosylated gangliosides, attractive targets for cancer immunotherapy as these glycolipids are not naturally expressed in humans. A clinical study with nonsmall cell lung cancer patients showed encouraging clinical benefits. Immunological studies performed in 20 of these patients suggested a correlation between the induction of Abs against NeuGcGM3 and longer survival times. The induced anti-NeuGcGM3 Abs recognized and directly killed tumor cells expressing the Ag, by a mechanism independent of complement activation. In the present work, we show that this cytotoxicity differs from apoptosis because it is temperature independent, no chromatin condensation or caspase 3 induction are detected, and the DNA fragmentation induced has a different pattern than the one characteristic for apoptosis. It is a very quick process and involves cytosqeleton reorganization. The Abs induce cellular swelling and the formation of big membrane lesions that allow the leakage of cytoplasm and the loss of the cell membrane integrity. All of these characteristics resemble a process of oncotic necrosis. To our knowledge, this is the first report of the active induction in cancer patients of NeuGcGM3-specific Abs able to induce complement independent oncotic necrosis to tumor cells. These results contribute to reinforcing the therapeutic potential of anti-idiotypic vaccines and the importance of NeuGcGM3 ganglioside as antitumor target.

[Use of the Cambridge Neuropsychological Test Automated Battery for the diagnosis of mild cognitive impairment. A pilot study in a Spanish sample]. / Utilización del CANTAB para el diagnóstico del deterioro cognitivo leve. Un estudio piloto con una muestra española.

INTRODUCTION: Suitable assessment tools for the diagnosis of mild cognitive impairment (MCI) could facilitate the early detection of Alzheimer's disease and other types of dementia. The aim of the present study was to assess the utility of the main memory and reaction time tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) for detecting MCI. MATERIAL AND METHODS: Episodic and working memory and reaction and movement times were tested in 16 MCI patients, classified according to Petersen's criteria, and in 15 healthy individuals. RESULTS: ANOVA showed that the performance of the MCI group was significantly poorer than that of the control group in movement time and episodic memory tests, pattern recognition, delayed matching to sample and paired associates learning. Performance in these tests correlated with the measures of general cognitive performance. However, the performance of both groups was similar in simple reaction times and in the spacial working memory tests. CONCLUSIONS: The CANTAB episodic memory tests and the movement time measures are effective instruments to detect MCI.

Utilización del CANTAB para el diagnóstico del deterioro cognitivo leve. Un estudio piloto con una muestra Española / Use of the Cambridge Neuropsychological Test Automated Battery for the diagnosis of mild cognitive impairment. A pilot study in a Spanish simple

Introducción: La disponibilidad de técnicas de evaluación adecuadas para el diagnóstico del deterioro cognitivo leve (DCL) puede facilitar la detección precoz de la enfermedad de Alzheimer (EA) y otras demencias. El objetivo de la presente investigación es estudiar la utilidad de las principales pruebas de memoria y de tiempos de reacción (TR) de la batería Cambridge Neuropsychological Test Automated Battery (CANTAB) en la detección del DCL. Material y métodos: Se aplicaron pruebas de memoria episódica, memoria operativa y TR a 16 sujetos con DCL, clasificados siguiendo los criterios de Petersen, y a 15 sujetos sanos. Resultados: Los análisis de varianza indicaron que el rendimiento del grupo con DCL fue significativamente peor que el del grupo control en los tiempos de movimiento y en las pruebas de memoria episódica, reconocimiento de patrones, emparejamiento retardado a patrones y aprendizaje de pares asociados. El rendimiento en estas pruebas se correlacionaba con las medidas en el rendimiento cognitivo general. No hubo diferencias en la prueba de memoria operativa espacial ni en los TR simples. Conclusiones: Las pruebas de memoria episódica del CANTAB y los tiempos de movimiento son buenos instrumentos para la detección del DCL (AU)

Introduction: Suitable assessment tools for the diagnosis of mild cognitive impairment (MCI) could facilitate the early detection of Alzheimer's disease and other types of dementia. The aim of the present study was to assess the utility of the main memory and reaction time tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) for detecting MCI. Material and methods: Episodic and working memory and reaction and movement times were tested in 16 MCI patients, classified according to Petersen's criteria, and in 15 healthy individuals. Results: ANOVA showed that the performance of the MCI group was significantly poorer than that of the control group in movement time and episodic memory tests, pattern recognition, delayed matching to sample and paired associates learning. Performance in these tests correlated with the measures of general cognitive performance. However, the performance of both groups was similar in simple reaction times and in the spacial working memory tests. Conclusions: The CANTAB episodic memory tests and the movement time measures are effective instruments to detect MCI (AU)

[Cognitive markers to discriminate between mild cognitive impairment and normal ageing]. / Discriminación mediante marcadores cognitivos del deterioro cognitivo leve frente a envejecimiento normal.

INTRODUCTION: mild cognitive impairment (MCI) has been characterized as a transitional stage between normal ageing and dementia. The aim of the present study was to examine differences between normal ageing and MCI in the performance of several cognitive tests. These differences might serve as differential markers. MATERIAL AND METHODS: we performed a longitudinal study (24 months) with two evaluations at 12-monthly intervals using the CAMCOG-R and a verbal learning test [test de aprendizaje verbal España-Complutense (TAVEC)]. The sample was composed of 25 persons aged more than 50 years old (five men and 20 women), distributed into two groups: the control group and the MCI group. To assign persons to either of the two groups, Petersen's MCI criteria were applied to Mini-Mental State Examination (MMSE) scores. RESULTS: repeated measures ANOVA (2 groups x 2 assessment) showed significant differences between the MCI and control group in the CAMCOG-R scores in orientation, language, memory, abstract thinking, executive function and global score and in the TAVEC scores for immediate recall and short- and long-term free and clued recall. No significant differences were found between the first and second assessment or in the interaction group assessment. CONCLUSIONS: the results of the present study confirm that the CAMCOG-R and the TAVEC effectively discriminate between normal ageing and MCI and can be used complementarily.

Discriminación mediante marcadores cognitivos del deterioro cognitivo leve frente a envejecimiento normal / The final week of life in an acute care hospital: review of 401 consecutive patients

Introducción: el deterioro cognitivo leve (DCL) se ha caracterizado como un estadio de transición entre el envejecimiento normal y la demencia. La presente investigación se propone estudiar las diferencias entre el envejecimiento normal y el DCL en la ejecución de varias pruebas cognitivas que puedan servir como marcadores discriminativos. Material y métodos: presentamos un estudio longitudinal (24 meses), con dos evaluaciones cada 12 meses en las que se aplicaron 2 pruebas, Cambridge Cognitive Assessment-Revised (CAMCOG-R) y test de aprendizaje verbal España-Complutense (TAVEC). La muestra fue de 25 sujetos, mayores de 50 años, 5 varones y 20 mujeres. Se formaron 2 grupos, control y DCL. Para la asignación de cada sujeto a cada grupo se aplicó el criterio de Petersen para el DCL a la puntuación obtenida en el Mini- Mental State Examination (MMSE). Resultados: los ANOVA de medidas repetidas (2 grupo × 2 evaluación) mostraron diferencias significativas entre los grupos DCL y control en las áreas de orientación, lenguaje, memoria, pensamiento abstracto, función ejecutiva y puntuación total en el CAMCOG, y en las variables sobre recuerdo inmediato, recuerdo libre y recuerdo con claves a corto y largo plazo del TAVEC. No aparecieron diferencias significativas entre la primera y la segunda evaluación, ni en la interacción grupo por evaluación. Conclusiones: tanto el CAMCOG-R como el TAVEC se confirman como buenos instrumentos para discriminar entre el envejecimiento normal y el DCL, y pueden utilizarse de forma complementaria

Introduction: mild cognitive impairment (MCI) has been characterized as a transitional stage between normal ageing and dementia. The aim of the present study was to examine differences between normal ageing and MCI in the performance of several cognitive tests. These differences might serve as differential markers. Material and methods: we performed a longitudinal study (24 months) with two evaluations at 12-monthly intervals using the CAMCOG-R and a verbal learning test [test de aprendizaje verbal España-Complutense (TAVEC)]. The sample was composed of 25 persons aged more than 50 years old (five men and 20 women), distributed into two groups: the control group and the MCI group. To assign persons to either of the two groups, Petersen¿s MCI criteria were applied to Mini-Mental State Examination (MMSE) scores. Results: repeated measures ANOVA (2 groups × 2 assessment) showed significant differences between the MCI and control group in the CAMCOG-R scores in orientation, language, memory, abstract thinking, executive function and global score and in the TAVEC scores for immediate recall and short- and longterm free and clued recall. No significant differences were found between the first and second assessment or in the interaction group assessment. Conclusions: the results of the present study confirm that the CAMCOG-R and the TAVEC effectively discriminate between normal ageing and MCI and can be used complementarily