Clinical landscape of LAG-3-targeted therapy.

Lymphocyte-activated gene 3 (LAG-3) is a cell surface inhibitory receptor and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. LAG-3 is considered a next-generation immune checkpoint of clinical importance, right next to programmed cell death protein 1 (PD-1) and cytotoxic T-cell lymphocyte antigen-4 (CTLA-4). Indeed, it is the third inhibitory receptor to be exploited in human anticancer immunotherapies. Several LAG-3-antagonistic immunotherapies are being evaluated at various stages of preclinical and clinical development. In addition, combination therapies blocking LAG-3 together with other immune checkpoints are also being evaluated at preclinical and clinical levels. Indeed, the co-blockade of LAG-3 with PD-1 is demonstrating encouraging results. A new generation of bispecific PD-1/LAG-3-blocking agents have also shown strong capacities to specifically target PD-1+ LAG-3+ highly dysfunctional T cells and enhance their proliferation and effector activities. Here we identify and classify preclinical and clinical trials conducted involving LAG-3 as a target through an extensive bibliographic research. The current understanding of LAG-3 clinical applications is summarized, and most of the publically available data up to date regarding LAG-3-targeted therapy preclinical and clinical research and development are reviewed and discussed.

[Test of the potency of trivalent oral polio vaccines: comparison of 2 methods of reading]. / Prueba de potencia de vacunas antipoliomielíticas orales trivalentes: comparación de dos métodos de lectura.

Trivalent oral poliovaccine is used in Argentina to prevent poliomyelitis. Its potency is tested by infectivity titration of the three viruses in susceptible cell cultures (Hep-2 cell line). In order to compare the conventional reading method of cytopathic effect (CPE) with the staining technique of cell monolayers with crystal violet-formol, the reference viruses and several lots of trivalent vaccines were titrated. Between 3 and 10 days post-infection (pi) the plates were read under microscope and immediately stained. The maximum viral titer was reached at 5-7 days pi and additional CPE after this period did not alter the results. An incomplete monolayer confluence or cell aging (6-7 days pi) resulted in a poor definition between positive and negative cultures when the staining test was used. By contrast, CPE was easily read by microscope observation. Therefore, the staining method should only be considered for vaccine titration as a possible alternative when an inverted microscope is lacking or a great number of plates has to be read. In this case, to stain at day 7 pi is recommended.

Prueba de potencia de vacunas antipoliomielíticas orales trivalentes: comparación de dos métodos de lectura. / [Test of the potency of trivalent oral polio vaccines: comparison of 2 methods of reading]

Trivalent oral poliovaccine is used in Argentina to prevent poliomyelitis. Its potency is tested by infectivity titration of the three viruses in susceptible cell cultures (Hep-2 cell line). In order to compare the conventional reading method of cytopathic effect (CPE) with the staining technique of cell monolayers with crystal violet-formol, the reference viruses and several lots of trivalent vaccines were titrated. Between 3 and 10 days post-infection (pi) the plates were read under microscope and immediately stained. The maximum viral titer was reached at 5-7 days pi and additional CPE after this period did not alter the results. An incomplete monolayer confluence or cell aging (6-7 days pi) resulted in a poor definition between positive and negative cultures when the staining test was used. By contrast, CPE was easily read by microscope observation. Therefore, the staining method should only be considered for vaccine titration as a possible alternative when an inverted microscope is lacking or a great number of plates has to be read. In this case, to stain at day 7 pi is recommended.