The role of chimeric antigen receptor T cells targeting more than one antigen in the treatment of B-cell malignancies.

Several products containing chimeric antigen receptor T cells targeting CD19 (CART19) have been approved for the treatment of patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL). Despite very impressive response rates, a significant percentage of patients experience disease relapse and die of progressive disease. A major cause of CART19 failure is loss or downregulation of CD19 expression in tumour cells, which has prompted a myriad of novel strategies aimed at targeting more than one antigen (e.

Academic challenges on advanced therapy medicinal products' development: a regulatory perspective.

Advanced therapy medicinal products (ATMPs) are becoming the new kid on the block for the treatment of a variety of indications with promising results. Despite the academic contribution to the basic and clinical research of ATMPs, undertaking a full product development process is extraordinarily challenging and demanding for academic institutions. Meeting regulatory requirements is probably the most challenging aspect of academic development, considering the limited experience and resources compared with pharmaceutical companies.

A Long Skip Connection for Enhanced Color Selectivity in CNN Architectures.

Some recent studies show that filters in convolutional neural networks (CNNs) have low color selectivity in datasets of natural scenes such as Imagenet. CNNs, bio-inspired by the visual cortex, are characterized by their hierarchical learning structure which appears to gradually transform the representation space. Inspired by the direct connection between the LGN and V4, which allows V4 to handle low-level information closer to the trichromatic input in addition to processed information that comes from V2/V3, we propose the addition of a long skip connection (LSC) between the first and last blocks of the feature extraction stage to allow deeper parts of the network to receive information from shallower layers.

NK cells enhance CAR-T cell antitumor efficacy by enhancing immune/tumor cells cluster formation and improving CAR-T cell fitness.

Background: Chimeric antigen receptor (CAR)-T cell immunotherapy has modified the concept of treatment in hematological malignancies. In comparison with pediatric patients, where responses are maintained over many years, older patients, such as those with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), present lower persistence of CAR-T cells that might be due to decreased fitness of T cells acquired with aging. Moreover, cord blood derived-NK cells (CB-NKs) and CAR-NK cells derived from CB-NK can be used 'off-the-shelf' as immune cells with antitumor properties for the treatment of cancer patients.