Human Immunology News Volume 5.03 | Jan 24 2017

TOP STORY

A Novel BCMA/CD3 Bispecific T-Cell Engager for the Treatment of Multiple Myeloma Induces Selective Lysis In Vitro and In Vivo

Investigators developed a bispecific T-cell engager targeting B-cell maturation antigen (BCMA) and CD3ε (BI 836909) and studied its therapeutic impacts on multiple myeloma (MM). BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. [Leukemia] Full Article

(Ranked by impact factor of the journal)

The Interplay between Neutrophils and CD8⁺ T Cells Improves Survival in Human Colorectal Cancer

Researchers investigated clinical relevance, phenotypes and functional features of colorectal cancer infiltrating CD66b⁺ neutrophils and their crosstalk with CD8⁺ T cells. [Clin Cancer Res] Abstract

Inducible Caspase9 Selectively Modulates the Toxicities of CD19-Specific Chimeric Antigen Receptor-Modified T Cells

Scientists demonstrated, in a humanized mouse model, that the inducible caspase9 safety switch can eliminate T-cells expressing the chimeric antigen receptor specific for the CD19 antigen (CD19.CAR-Ts) in a dose dependent manner, allowing either a selective containment of CD19.CAR-T expansion in case of cytokine release syndrome or complete deletion on demand granting normal B-cell reconstitution. [Mol Ther] Abstract | Full Article

The Immunoglobulin Superfamily Member CD200R Identifies Cells Involved in Type 2 Immune Responses

The authors identified surface markers associated with type 2 inflammation. Naïve human CD4⁺ T-cells were short-term activated in the presence or absence of IL-4, and analyzed for expression of >300 cell-surface proteins. [Allergy] Abstract

An Altered Endometrial CD8 Tissue Resident Memory T Cell Population in Recurrent Miscarriage

Researchers characterized the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress. [Sci Rep] Full Article

IL-22-Producing CD4⁺T Cells in the Treatment Response of Rheumatoid Arthritis to Combination Therapy with Methotrexate and Leflunomide

Scientists monitored circulating levels of different interleukin (IL)-22⁺ T helper cell subsets and measured plasma levels of IL-22, IL-17, and interferon-γ in 60 patients with active rheumatoid arthritis following 12-week combination methotrexate and leflunomide therapy and 20 healthy individuals. [Sci Rep] Full Article

Activation of Human B Cells Negatively Regulates TGF-β1 Production

Scientists compared B cell production of transforming growth factor (TGF)-β1 and interleukin (IL)-10, the two most studied regulatory cytokines, and the pro-inflammatory B cell-derived IL-6 and tumor necrosis factor cytokines under basal conditions and following polyclonal stimulation with dual B cell receptor cross-linking and Toll-like receptor 9 engagement. [J Neuroinflammation] Full Article

Properdin and Factor H Production by Human Dendritic Cells Modulates their T-Cell Stimulatory Capacity and Is Regulated by IFN-γ

Researchers investigated the production and regulation of properdin (fP) and factor H (fH), both integral regulators of the alternative pathway (AP), by dendritic cells (DCs) and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs. [Eur J Immunol] Abstract

A High Migratory Capacity of Donor T-Cells in Response to the Lymph Node Homing Receptor CCR7 Increases the Incidence and Severity of GvHD

The authors investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor–recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. [Bone Marrow Transplant] Abstract

The Distribution and Function of Human Memory T Cell Subsets in Lung Cancer

The authors investigated the properties of human T cell subsets in the blood of non-small cell lung cancer (NSCLC) patients. They found a relatively normal level of CD4⁺ subsets in the blood of NSCLC patients, but CD8⁺ effector T cells increased and CD8⁺ effector memory cells declined compared to the healthy donors. [Immunol Res] Full Article

Defective T-Cell Control of Epstein–Barr Virus Infection in Multiple Sclerosis

Investigators undertook a comprehensive analysis of the T-cell response to Epstein–Barr virus (EBV) in multiple sclerosis, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus, in 95 patients and 56 EBV-seropositive healthy subjects. [Clin Transl Immunology] Full Article

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Is Immunotherapy Here To Stay In Multiple Myeloma?

The authors discuss the current results obtained with immune approaches in patients with multiple myeloma that have placed this disease under the scope of immune-oncology bringing new therapeutic opportunities for the treatment of multiple myeloma patients. [Haematologica] Abstract

T-Cell Receptor-Engineered T Cells for Cancer Treatment: Current Status and Future Directions

Researchers provide a perspective on the current and future applications of T-cell receptor (TCR)-engineered T cells for the treatment of cancer. They focus on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. [Protein Cell] Abstract

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Infinity Presents Preclinical Data and Phase I Clinical Data on IPI-549

Infinity Pharmaceuticals, Inc. presented preclinical data for IPI-549, an oral immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase-gamma. [Press release from Infinity Pharmaceuticals, Inc. discussing research presented at the Keystone Symposia Conference – PI3K Pathways in Immunology, Growth Disorders and Cancer, Santa Fe] Press Release

Immune Pharmaceuticals Enters a Research Partnership to Develop Mono- and Bispecific Antibodies against Novel Targets in the Tumor Microenvironment

Immune Pharmaceuticals Inc. announced that it has entered an exclusive sub-license agreement with SATT Sud-Est to develop, use, manufacture and commercialize mono- and bispecific antibodies targeting components of the tumor microenvironment and angiogenic factors. [Immune Pharmaceuticals Inc.] Press Release

ASIT biotech Announces Last Patient Last Visit in the Phase IIa Clinical Study with Its hdm-ASIT⁺™ Product Candidate for Treating House Dust Mite Rhinitis

ASIT biotech announced that its Phase IIa double-blind placebo-controlled clinical study in house dust mite-induced rhinoconjunctivitis has completed its clinical phase. [ASIT biotech] Press Release

Biotech Firm Backs Controversial CRISPR Challenger

A major enzyme manufacturer has signed an agreement with a Chinese university to explore uses for a protein claimed to be a powerful alternative to the popular genome-editing tool CRISPR–Cas9. Several scientists have failed to reproduce the results of the paper that first made the claim and doubt that the protein, NgAgo, works as a gene editor. [Nature News] Editorial

Scientists Join Massive Protest against Trump

The women in white lab coats didn’t expect to be treated like celebrities. The group of scientists, dozens strong, came to Washington DC to join the Women’s March, a massive protest against the brand-new US President, Donald Trump. But as they navigated the dense crowd near the National Air and Space Museum, the researchers were greeted by shouts of “We love science!” Eager strangers asked the scientists to pose for photographs with the signs they carried, which bore slogans such as “Stand up 4 Science” and “Science does not discriminate.” [Nature News] Editorial

Wanted: A Leader for the Toughest Job in Global Health

Global health watchers will pay close attention to Geneva, Switzerland when the World Health Organization (WHO) will announce the final three candidates to take the agency’s top job. The decision by WHO’s Executive Board, made up of representatives of 34 member states, follows months of behind-the-scenes jockeying, campaigning by the candidates, and intense speculation. It will be followed in May by a final vote by WHO’s 194 member states. [ScienceInsider] Editorial

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