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Resources for DIU Immunologie et Biothérapies
DIU Immunologie et Biotherapies is a french diploma associating many french universities and immunology laboratories. It is dedicated to the involvement of immunology in new biotherapies, either molecular or cellular
Engineered cytokines are able to improve immunotherapy in mouse tumor models.
Immune checkpoint therapy can induce durable remissions, but many tumors demonstrate
resistance. In a recent issue of Nature, Mariathasan et al. (2018) and Tauriello et al.
(2018) identify stromal TGF-β signaling as a determinant of immune exclusion. Combination
TGF-β inhibition and immunotherapy induces complete responses in mouse models.
Creative Biogene has developed CAR lentiviral packaging service based on most advanced techniques and extensive experience.
There are no vaccines or therapies to treat Epstein-Barr virus (EBV). Snijder et al.
(2018) isolated a potent human antibody against EBV that blocks infection of both
B cells and epithelial cells. Structural analysis of the antibody complexed with a
viral surface protein complex identified a site that may be useful in vaccine development.
The field of cancer immunotherapy is no longer in its infancy. Two lines of progress in clinical research are achieving true clinical success: (i) checkpoint blockade for solid tumors and (ii) chimeric antigen receptor (CAR) T-cell therapy for lymphoid malignancies ([1][1]). Clinical Cancer Research
BioCentury’s analysis of new and emerging targets presented at this year’s AACR meeting reveals a surge in activity in non-coding RNAs, as researchers continue to expand target space. The results also reflect the ongoing high level of interest in finding new ways to manipulate immune cells.
Natural killer (NK) cells perform immune surveillance for virally infected cells and tumor cells. The balance between the engagement of activating receptors, such as NKG2D, and inhibitory receptors on the NK cell surface determines whether the cells kill their targets. Through superresolution microscopy, Bálint et al . showed that NKG2D on the surface of unstimulated NK cells was organized into nanoclusters, which became differentially reorganized depending on whether the cells were exposed to MICA or ULBP2, two NKG2D ligands found on tumor cells. Stimulation with ULBP2, but not MICA, caused NKG2D to cluster with the receptor for the cytokine IL-15, which can also be presented on tumor cells, synergizing with NKG2D to enhance NK cell responses. These data suggest that NKG2D ligands have distinct outcomes on NK cell function, which may have relevance in the use of NK cells as an immunotherapy.
Cell Press, working in conjunction with the Molecular Therapy family of journals, has created an editorially curated collection of articles that highlights the current state of the art in the development of CAR T cell therapies.
Via Krishan Maggon
Adoptive cellular therapy using T cells with tumor specificity derived from either
natural T cell receptors (TCRs) or an artificial chimeric antigen receptor (CAR) has
reached late phase clinical testing, with two CAR T cell therapies achieving regulatory
approval within the United States in 2017. The effective use of these therapies depends
upon an understanding of their pharmacology, which is quite divergent from traditional
small molecule or biologic drugs. We review the different types of T cell therapy
under clinical development, the factors affecting cellular kinetics following infusion,
and the relationship between these cellular kinetics and anti-cancer activity.
Vanderbilt investigators have discovered that cancer treatment induces an “idling” state for cells, which could promote resistance to treatment.
Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.
Mice treated with an immunostimulant had better outcomes when researchers blocked the expression of TNFR2, a compound that helps tumors evade immune attack.
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Format: AbstractSend to J Am Acad Dermatol. 2017 Dec 26. pii: S0190-9622(17)32890-6. doi: 10.1016/j.jaad.2017.12.050. [Epub ahead of print] Dermatologic manifestations of solid organ transplantation-associated graft-versus-host disease: A systematic review. Kim GY1, Schmelkin LA2, Davis MDP3, El-Azhary RA3, Farrell AM4, Meves A3, Lehman JS5. Author information 1 Mayo Clinic School of Medicine, Rochester, MN, USA. 2 Mayo Clinic School of Graduate Medical Education, Mayo Clinic, Rochester, MN, USA. 3 Department of Dermatology, Mayo Clinic, Rochester, MN, USA. 4 Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA. 5 Department of Dermatology, Mayo Clinic, Rochester, MN, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address: lehman.julia@mayo.edu. KEYWORDS: Graft-versus-host disease; dermatopathology; transplant PMID: 29288097 DOI: 10.1016/j.jaad.2017.12.050 PubMed Commons home PubMed Commons 0 comments How to join PubMed Commons
Arce Vargas et al. use a mouse model expressing human FcγRs to show that antibodies
with isotypes equivalent to ipilimumab increase the CD8+ to Treg ratio by depleting
intra-tumoral Tregs to promote tumor rejection. In melanoma patients, response to
ipilimumab is associated with a high affinity FcγR polymorphism.
No company has made a larger bet on using human genetics to drive R&D than Amgen. Here’s an update on the company’s quest to focus its research on targets validated in humans.
The presence of cancer stem cells (CSCs) is one of the main reasons that cause cancer
relapse and metastasis. In this study, NF-κB shRNA was delivered to target CSCs using
carbamate-mannose modified PEI (CMP) as a non-viral gene vector. The polymer was synthesized
by blocking primary amine groups of branched PEI (10kDa) through nucleophilic addition
between PEI and protected mannose-functionalized cyclic carbonate, followed by mannose
deprotection. CMP/control shRNA nanocomplexes showed lower cytotoxicity and higher
transfection efficiency in 4T1 murine breast cancer cells than unmodified PEI/control
shRNA nanocomplexes.
The scientific rationale behind immunotherapies in oncology, and how partnerships, co-marketing and positioning will shape the market in pharma.
Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune
responses can regress tumors. However, this only occurs in a fraction of patients.
Incorporating these therapies in more powerful combinations is thus a logical next
step. Here, we review functional roles of immune checkpoints and molecular determinants
of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors,
differing substantially from “self,” generally respond to checkpoint blockade. Therefore,
we propose that reducing tumor burden and increasing tumor immunogenicity are key
factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy
combination partners and highlight the importance of activity biomarkers for timely
treatment optimization.
AAAAI's Ask the Expert talks about IVIG indications: hypogammaglobulinemia & peripheral neuropathy.
Dermatol Ther (Heidelb). 2018 Apr 6. doi: 10.1007/s13555-018-0235-4. [Epub ahead of print] Review
The concept of exploiting the specific binding properties of monoclonal antibodies as a mechanism for selective delivery of cytotoxic agents to tumor cells is an attractive solution to the challenge of increasing the therapeutic index of cell-killing agents for treating cancer.
Via Krishan Maggon
This study demonstrates that IL13Rα2-targeted CAR-modified T cells have anti-tumor
activity in immunocompetent glioma models. While CAR T cells reversed the immunosuppressive
glioma microenvironment, their effector function was eventually eroded. These results
provide the rationale to explore combinatorial therapies or additional genetic modifications
to enhance the anti-glioma activity of CAR T cells.
A new type of cancer vaccine has yielded promising results in an initial clinical trial conducted at the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center of the University of Pennsylvania
Watch this informative Nature video, which describes how the immune system interacts with a tumour and how immunotherapy treatments are designed to work.
Lung cancer is a leading cause of cancer-related death among both men and women in the United States, where non–small cell lung cancer accounts for ∼85% of lung cancer. Lung adenocarcinoma (ADC) is the major histologic subtype. The presence of actionable mutations prompts the use of therapies designed to specifically address the deleterious effects of those cancer-driving mutations; these therapies have already shown promise in cases carrying those actionable mutations (∼30%). Innovative therapeutic approaches are needed for the treatment of 70% of patients suffering from lung ADC. Adoptive transfer of CD8+ T cells specific against cancer/testis (CT) Ags, whose protein expression is restricted to the gonads (testis and ovary) and cancerous cells, is an excellent alternative. In this study, we report the isolation of HLA-A*02:01/CT37 peptide–specific α and β TCR chains from a CD8+ T cell clone obtained from a patient suffering from lung ADC. We also report the development of an innovative CD3ζ construct. With those TCR chains and the engineered (modified) CD3ζ chain, we produced a construct that when transduced into CD8+ T cells is capable of redirecting transduced CD8+ T cell cytotoxic activity and IFN-γ secretion against peptide-pulsed autologous cells and HLA-A*02:01 –positive and CT37-expressing lung ADC cell lines. Our findings will launch the development of innovative adoptive transfer immunotherapies for the treatment of lung ADC, targeting the most prevalent HLA molecules and CT37 peptides restricted by these molecules.
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