Whole tumour cell-based vaccines: tuning the instruments to orchestrate an optimal antitumour immune response.

Immunotherapy, particularly those based on immune checkpoint inhibitors (ICIs), has become a useful approach for many neoplastic diseases. Despite the improvements of ICIs in supporting tumour regression and prolonging survival, many patients do not respond or develop resistance to treatment. Thus, therapies that enhance antitumour immunity, such as anticancer vaccines, constitute a feasible and promising therapeutic strategy. Whole tumour cell (WTC) vaccines have been extensively tested in clinical studies as intact or genetically modified cells or tumour lysates, injected directly or loaded on DCs with distinct adjuvants. The essential requirements of WTC vaccines include the optimal delivery of a broad battery of tumour-associated antigens, the presence of tumour cell-derived molecular danger signals, and adequate adjuvants. These factors trigger an early and robust local innate inflammatory response that orchestrates an antigen-specific and proinflammatory adaptive antitumour response capable of controlling tumour growth by several mechanisms. In this review, the strengths and weaknesses of our own and others' experiences in studying WTC vaccines are revised to discuss the essential elements required to increase anticancer vaccine effectiveness.

Validación y aplicación de un ELISA para la cuantificación de anticuerpos IgG contra polisacárido capsular Vi de Salmonella Typhi / Validation and application of an ELISA for the quantification of IgG antibodies against Salmonella Typhi Vi capsular polysaccharide

Como parte de las etapas de investigación y desarrollo de un candidato vacunal conjugado contra Salmonella Typhi, se desarrolló un ELISA indirecto para la cuantificación de anticuerpos IgG contra el polisacárido Vi de esta bacteria. En este trabajo se presentan los resultados del proceso de validación, en el que se determinaron el intervalo y linealidad de la curva, la precisión intra e interensayo, la exactitud, la especificidad, el límite de detección y la robustez. La curva de calibración, generada con un suero estándar interno, presentó un buen ajuste a una función polinómica y un intervalo entre las diluciones 1/100 y 1/3200. Los coeficientes de variación en los ensayos de precisión y robustez y los porcentajes de recobrado estuvieron en los intervalos establecidos para cada uno (≤10 por ciento, ≤20 por ciento y 90-110 por ciento respectivamente). El ensayo presentó una especificidad óptima, obteniéndose señales de DO superiores a 1,3 para sueros positivos contra Vi y bajas para sueros contra antígenos no relacionados. Los resultados avalan el empleo de este ELISA cuantitativo en ensayos de inmunogenicidad para la liberación de lotes de conjugados de Vi. Igualmente, sustentan su uso para la evaluación de la inmunogenicidad de formulaciones de polisacárido Vi y conjugados de polisacárido Vi a proteínas en fases de investigación y desarrollo(AU)

An indirect ELISA for the quantification of IgG antibodies against the Vi polysaccharide of this bacteria was developed as a part of the stages of Research and Development of a conjugate vaccinal candidate against Salmonella Typhi. The results of the validation process are presented in this paper, in which the interval and linearity of the curve, the intra- and inter-assay precision, accuracy, specificity, limit of detection and robustness were determined. The calibration curve generated with an internal standard serum provided a good fit to a polynomial function and an interval between 1/100 and 1/3200 dilutions. The coefficients of variation in the precision and robustness tests and the percentages of recovery were in intervals established for each one (≤10 percent, ≤20 percent and 90-110 percent, respectively). The assay presented an optimal specificity, obtaining OD signals above 1.3 for positive sera against Vi and low for sera against unrelated antigens. The results support the use of this quantitative ELISA in immunogenicity assays for batch release of Vi conjugates. Likewise, they support their use for the immunogenicity evaluation of Vi polysaccharide formulations and Vi polysaccharide conjugates to proteins in phases of research and development(AU)