Anti-CD19 Monoclonal antibody, clone IJC20 [APC-eFluor® 780]

Therapies that bind with immune cells and redirect their cytotoxic activity toward diseased cells represent a promising and versatile approach to immunotherapy with applications in cancer, lupus, and other diseases; traditional methods for discovering these therapies, however, are often time-intensive and lack the throughput of related target-based discovery approaches. Inspired by the observation that the cytokine, IL-12, can enhance antileukemic activity of the clinically approved T cell redirecting therapy, blinatumomab, here we describe the structure and assembly of a chimeric immune cell-redirecting agent which redirects the lytic activity of primary human T cells toward leukemic B cells and simultaneously cotargets the delivery of T cell-stimulating IL-12. We further describe a novel method for the parallel assembly of compositionally diverse libraries of these bispecific T cell engaging cytokines (BiTEoldnes) and their high-throughput phenotypic screening, requiring just days for hit identification and the analysis of composition-function relationships. Using this approach, we identified CD19 x CD3 x IL12 compounds that exhibit ex vivo lytic activity comparable to current FDA-approved therapies for leukemia and correlated drug treatment with specific cell-cell contact, cytokine delivery, and leukemia cell lysis. Given the modular nature of these multivalent compounds and their rapid assembly/screening, we anticipate facile extension of this therapeutic approach to a wide range of immune cells, diseased cells, and soluble protein combinations in the future.

Immunocompromised patients may be at increased risk to develop COVID-19 during the 2019 beta-coronavirus infection. We present the unique opportunity we had to monitor the liver, IL-6 and immune cell course before, during and after COVID-19 in a boy with autoimmune hepatitis (AIH) and type 1 diabetes (T1D). CD4(+)and CD8(+)T cells frequencies decreased because of prednisolone, followed by a plateauing increase whereas CD19(+)CD20(+)B cell increased strongly and was unaffected by COVID-19 infection. Moreover, the percentage of activated CD8(+)T cells expressing HLA-DR (CD8(+)HLA-DR+) increased during COVID-19 and subsided after its clearance. Total regulatory T cells (Tregs: CD4(+)CD25(+)CD127(low)FOXP3(+)) remained stable. Although activated Tregs (CD4(+)CD45RA(-)FOXP3(high)) strongly increased upon prednisolone, it decreased afterwards. Furthermore, regulatory B cells (Bregs: CD19(+)CD20(+)CD24(high)CD38(high)) declined sharply owing to prednisolone. Serum IL-6 remained undetectable at all times. We demonstrated for the first time immune monitoring in a child with AIH and T1D before, during and after COVID-19. We hypothesize that continuing with low level of prednisolone without azathioprine may have abrogated activated Tregs, Bregs and IL-6 production and therefore permitting the activation of CD8(+)T cells, clearing the virus. Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved.