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Scooped by Gilbert Faure au nom de l'ASSIM from Cancer Immunotherapy Review
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Mast cells as targets for immunotherapy of solid tumors

Mast cells as targets for immunotherapy of solid tumors | Immunology and Biotherapies | Scoop.it

Highlights

 

Mast cells are found in large numbers at solid tumor sites and can have both pro-tumorigenic and anti-tumorigenic roles.

Multiple pathways, including hypoxia, adenosine, TLR, antibody and complement, can activate mast cells in solid tumors.

Activated mast cells recruit immune effector and regulatory cells and mobilize dendritic cell responses.

Mast cells are excellent targets for cancer immunotherapy due to their location, prolonged lifespan and radio-resistance.

 

Abstract

Mast cells have historically been studied mainly in the context of allergic disease. In recent years, we have come to understand the critical importance of mast cells in tissue remodeling events and their role as sentinel cells in the induction and development of effective immune responses to infection. Studies of the role of mast cells in tumor immunity are more limited. The pro-tumorigenic role of mast cells has been widely reported. However, mast cell infiltration predicts improved prognosis in some cancers, suggesting that their prognostic value may be dependent on other variables. Such factors may include the nature of local mast cell subsets and the various activation stimuli present within the tumor microenvironment. Experimental models have highlighted the importance of mast cells in orchestrating the anti-tumor events that follow immunotherapies that target innate immunity. Mast cells are long-lived tissue resident cells that are abundant around many solid tumors and are radiation resistant making them unique candidates for combined treatment modalities. This review will examine some of the key roles of mast cells in tumor immunity, with a focus on potential immunotherapeutic interventions that harness the sentinel role of mast cells.


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Krishan Maggon 's curator insight, October 13, 11:46 AM
Molecular Immunology

Volume 63, Issue 1, January 2015, Pages 113–124

Mast cell biology: new functions for an old cell

Review Mast cells as targets for immunotherapy of solid tumors ☆Sharon A. Oldforda, b, Jean S. Marshalla, b, ,   Show moreDOI: 10.1016/j.molimm.2014.02.020Under a Creative Commons DMCC
Scooped by Gilbert Faure au nom de l'ASSIM from Cancer Immunotherapy Review
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Immunotherapy top 5 indications in clinical trials

Immunotherapy top 5 indications in clinical trials | Immunology and Biotherapies | Scoop.it

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Krishan Maggon 's curator insight, July 19, 5:11 PM

The top 5 cancer types listed by the number of immunotherapy clinical trials, derived from ClinTrials.gov

 

Neoplasm Glandular/Epithelial     228

Neoplasm Nerves                                203

Carcinoma                                              192

Melanoma                                               127

Leukemia                                                  108

 

 

Gilbert Faure au nom de l'ASSIM's comment, July 20, 3:42 AM
nice synthesis! I had recently a similar idea to write "capsules" on topics of interest
Krishan Maggon 's comment, July 21, 10:17 AM
Very good idea, i wish there was a way to collaborate and place for collaborative efforts. thanks and best regards
Scooped by Gilbert Faure au nom de l'ASSIM from Top Selling Monoclonal Antibodies 2013
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Best Selling Monoclonal Antibodies 2013

Best Selling Monoclonal Antibodies 2013 | Immunology and Biotherapies | Scoop.it

Via Krishan Maggon
Gilbert Faure au nom de l'ASSIM's insight:

impressive for immunologists so far away from so big amounts of money

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Krishan Maggon 's curator insight, January 6, 8:38 AM

Abstract

 

A review of the best selling monoclonal antibodies in 2013 and 2012 is provided. Humira with sales of over $11 billion ($9.3 billion in 2012) remains the best selling monoclonal antibody, biologic as well prescription drug brand in 2013 as in 2012. The ranks of the next 4 top selling mabs remained unchanged from the 2012 Table.  Remicade (9.7 Bn), Rituxan (7.5 Bn) , Herceptin (6.5 Bn) and Avastin (6.5 Bn) were the second, third, fourth and fifth top selling mabs in 2013. The actual sales for 2013 as reported by the companies are provided. The total sales of the top selling blockbuster mabs were $63 billion in 2013. The actual global sales of all the approved blockbuster sales or potential (sales >1 billion) monoclonal antibodies in 2013 is provided. Besides the top 5 mabs, there were 2 other monoclonal antibodies with sales of over 2 billion dollars and 5 with sales of over $ 1 billion in 2013. In addition 5 recently launched mabs were nearing to reach sales of $ 1 billion this year. Currently 30 monoclonal antibodies are marketed in the US and Europe (January 2014).  Alexion Soliris was the most expansive marketed monoclonal antibody with a price tag of $440,000 per year of treatment, a sort of Rolls-Royce of mabs.

 

Scooped by Gilbert Faure au nom de l'ASSIM from Cancer Immunotherapy Review
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Tumor Infiltrating Lymphocytes (TIL) : Lion Biotechnologies

Tumor Infiltrating Lymphocytes (TIL) : Lion Biotechnologies | Immunology and Biotherapies | Scoop.it

TIL Technology 

In the early stages of cancer, special immune cells known as tumor infiltrating lymphocytes (TILs) migrate to the tumor and launch an attack.  However, this effect is usually short-lived because cancer adapts to evade immune detection and suppress immune response. Lion’s TIL technology is designed to overcome the immunosuppressive effects of cancer, while leveraging and enhancing the power of TILs to treat, and potentially cure, all solid tumors.

Our TIL technology has demonstrated robust efficacy in Phase 2 clinical trials, indicating objective response rates of 49% in Stage 4 metastatic melanoma.  Based on an adoptive cell therapy regimen developed by Steven A. Rosenberg, MD, chief of surgery at National Cancer Institute (NCI), it is currently in use as a physician-sponsored investigational treatment for Stage IV metastatic melanoma at NCI, MD Anderson Cancer Center, and the H. Lee Moffitt Cancer & Research Institute.


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Gilbert Faure au nom de l'ASSIM's insight:

TIL back on stage? they are not in memories of most students

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Krishan Maggon 's curator insight, July 23, 10:13 PM

Lion Biotech TIL is in Phase II trials in advanced metastatic melanoma and in Phase I trials in combination with BRAF inhibitor Zelboraf (vemurafenib, Roche) and in another Phase I with Yervoy (Ipilimumab, BMS). all trials are with NCI.

Scooped by Gilbert Faure au nom de l'ASSIM from Cancer Immunotherapy Review
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Cellectis French touch in Cancer Immunotherapy attracts Pfizer

Cellectis French touch in Cancer Immunotherapy attracts Pfizer | Immunology and Biotherapies | Scoop.it

Engineered T cell CAR therapy

 

A revolution is taking place in the field of adoptive immunotherapy, where T cells armed with a Chimeric Antigen Receptor (CAR) are being used to fight cancerous cells. Genome engineering is at the heart of this revolution. This groundbreaking technology relies mainly on the use of engineered nucleases and makes it possible to modify the genome of the T cell to give it new properties. Specifically, the engineered T cell can be transformed into an allogeneic product, or it can resist existing cancer treatments or even overcome checkpoint inhibition. Genome engineering is regarded as one of the most important breakthroughs of recent years, and is about to revolutionize immunotherapy. 

Decades of research have shown that it is possible to improve the ability of T cells to fight diseases by genome engineering. For example, T cells can be engineered by adding a new gene (called a chimeric antigen receptor or CAR) that will boost their ability to recognize and destroy cancer cells. Another possibility for T cells is to inactivate an existing gene that damages the immune response.

The possibilities provided by T cell genome engineering are endless. Very sophisticated strategies can be designed at will to open the door for a new era of treatments in indications such as infectious diseases, autoimmune diseases, and cancer.

 

Chimeric Antigen Receptors (CARs) are artificial molecules that, when present at the surface of immune effector cells, will enable them to recognize a desired protein (antigen) and trigger the killing of cells harboring this antigen at their surface (target cells).

These receptors are becoming one of the most promising approaches to fight cancer, through the development of adoptive cell transfer therapies. Indeed, immune cells (most usually T-lymphocytes) can be engineered to express a CAR able to recognize proteins present at the surface of cancer cells. Upon cell-to-cell contact between effector and targeted cells, antigen recognition will activate the effectors, giving them the signal to attack their targets, and leading ultimately to the killing of cancer cells.

CARs are constructed by assembling domains from different proteins, each of which enables the chimeric molecule to carry out specific functions. The most common CAR architecture comprises an extracellular domain containing a region that recognizes the targeted antigen and a spacer region that links it to the transmembrane domain (the part of the protein that spans the cellular membrane). This is then followed by an intracellular domain, responsible for transmitting an activation signal to the cell upon antigen recognition, causing the CAR-engineered cell to attack the tumor cell.

The target-binding moiety is usually derived from an antibody, while the intracellular portion can include, besides the domain leading to cell activation and cytotoxic response, one or more domains from co-stimulatory receptor proteins that could enhance the proliferative capacity and survival of the “therapeutic” cells.

Cellectis is currently developing a collection of CARs targeting antigens present on cells from various types of cancer, as well as a proprietary multi-chain architecture of these artificial receptors, aiming to further increase the efficacy of adoptive cell therapies in the future.





CELLECTIS’ UCART19 RECEIVES ADVANCED-THERAPY MEDICINAL PRODUCT CLASSIFICATION FROM EMAJune 23, 2014

 

READ MORE READ THE PRESS RELEASEPFIZER AND CELLECTIS ENTER INTO GLOBAL STRATEGIC CANCER IMMUNOTHERAPY COLLABORATIONJune 18, 2014 


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Krishan Maggon 's comment, July 16, 11:24 AM
thanks a lot, I think this is an important development and a big vote of confidence from big pharma in Cellectis CAR and bioengineered T cells. Great day for French R&D and start up companies in Immunotherapy.
Krishan Maggon 's comment, July 16, 11:26 AM
I wonder why the total number of visitors and page view remains too low. I think it is the absence from the USA market of Scoop it?
Gilbert Faure au nom de l'ASSIM's comment, July 16, 12:05 PM
what are you refereeing to? I will send you the draft of a summary for a meeting Science&You next year where I want to submit a talk or a session about curation. Check your e-mail to-morrow.