Cancer Immunotherapy Review
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Cancer Immunotherapy Review
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Ipilimumab (BMS) Review: A Cancer Breakthrough? - un knol de Krishan Maggon

Ipilimumab (BMS) Review: A Cancer Breakthrough? - un knol de Krishan Maggon | Cancer Immunotherapy Review | Scoop.it
FDA has approved Yervoy (ipilimumab, BMS) under REMS for the treatment of metastatic melanoma. The European expert panel CHMP...
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Advances in Immunotherapy: Using an Antibiotic to Remote-control CAR T cells - CANCER RESEARCH Catalyst

Advances in Immunotherapy: Using an Antibiotic to Remote-control CAR T cells - CANCER RESEARCH Catalyst | Cancer Immunotherapy Review | Scoop.it
A study published recently in the AACR’s journal Cancer Immunology Research describes an important update to the CAR T-cell technology, in which researchers have devised a mechanism to turn th
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Immune Checkpoint Inhibitors: Boosting the Cancer Battle

Immune Checkpoint Inhibitors: Boosting the Cancer Battle | Cancer Immunotherapy Review | Scoop.it
Overview of cancer treatment with the novel immune checkpoint inhibitors including Keytruda, Opdivo, Yervoy, and Tecentriq.
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Quantitative Comparison of Antibodies to PD-L1

Quantitative Comparison of Antibodies to PD-L1 | Cancer Immunotherapy Review | Scoop.it
Research from JAMA Oncology — A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1

Abstract

Importance Assessment of PD-L1 (programmed cell death 1 ligand 1) expression by immunohistochemical analysis has been used as a predictive diagnostic test to identify responders and guide treatment in trials of the PD-1 (programmed cell death 1) axis inhibitors. The definition of PD-L1 positive lacks standardization, and prediction of response by immunohistochemical analysis is additionally limited by the subjective nature of this technique. 

 Objective To examine whether PD-L1 antibody reagents are interchangeable by quantitatively comparing the expression of the PD-L1 protein. Design, Setting, and Participants In this immunohistochemistry standardization study, 30 randomly selected cases of lung cancer resected from January 1, 2008, through December 31, 2009, were obtained from Yale Pathology Archives with a range of expression of PD-L1. To test for protein measurement, rather than clinical utility, a PD-L1 index tissue microarray, including cell line and tissue controls, was used. The results were then validated on a commercially available, genetically defined PD-L1 engineered cell line array with a range of controlled protein-expressing cell lines using 6 monoclonal antibodies (SP142, E1L3N, 9A11, SP263, 22c3, and 28-8). Protein levels were measured by quantitative immunofluorescence and quantitative chromogenic assessment. Data analysis was performed from September 2015 through May 2016. 

 Results Concordance between 4 antibodies revealed regression for tumor tissue cores (R2 = 0.42-0.91) and cell line cores (R2 = 0.83-0.97) by quantitative immunofluorescence in the PD-L1 index tissue microarray. All 6 antibodies had high levels of concordance (R2 = 0.76-0.99) when using chromogenic staining in isogenic cell lines. 

Conclusions and Relevance Because the antibodies are highly concordant, these results suggest that assays based on the use of these antibodies could yield concordant results. They further suggest that previously described differences in PD-L1 expression in tissue are independent of the antibody used and likely attributable to tumor heterogeneity, assay- or platform-specific variables, or other factors.
Krishan Maggon 's insight:
A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1 ONLINE FIRST 

Patricia Gaule, PhD1; James W. Smithy, BS1; Maria Toki, MD1; Jamaal Rehman, MD1; Farah Patell-Socha, PhD2; Delphine Cougot, PhD2; Philippe Collin, PhD2; Paul Morrill, PhD2; Veronique Neumeister, MD1; David L. Rimm, MD, PhD1 
[+] Author Affiliations 

JAMA Oncol. Published online August 18, 2016. doi:10.1001/jamaoncol.2016.3015
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Engineered T cells: the promise and challenges of cancer immunotherapy

Engineered T cells: the promise and challenges of cancer immunotherapy | Cancer Immunotherapy Review | Scoop.it
Nature Reviews Cancer | doi:10.1038/nrc.2016.97


Tcell receptors (TCRs) provide a recognition signal for Tcells complemented by a co-stimulatory signal that can provide an on/off signal to regulate the activation of Tcells (FIG.1). Naturally occurring immune responses against cancer have been described1; however, inherent to a persistent cancer is the ability to overcome such immune control. Since Medawar and colleagues2 carried out their seminal work, it has long been recognized that adoptively transferred Tcells have the potential to target and destroy cancer cells. In some cases, however, trans-ferred Tcells lacked sufficient specificity or numbers to completely reject atumour3–5. Tcells genetically engi-neered to express novel receptors have enhanced tumour specificity. In addition, advances in exvivo expansion enable the production of clinically relevant doses of these therapeutic cells. Engineered Tcells have produced unprecedented results in the clinic.The earliest clinical trials of engineered Tcells in cancer relied on the expression of cloned TCRs with tar-geted affinity for tumour antigens. A TCR may recognize either intracellular or extracellular antigen in the context of major histocompatibility complex (MHC) presentation. When designing a TCR to target tumour cells, having the option to target intracellular tumour antigen may be advantageous as this may expand the pool of potential targets. 
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European Medicines Agency - Addressing challenges of innovative cancer immunotherapy medicines

European Medicines Agency - Addressing challenges of innovative cancer immunotherapy medicines | Cancer Immunotherapy Review | Scoop.it

EMA workshop to discuss treatments based on genetically modified T-cells The European Medicines Agency’s (EMA) Committee for Advanced Therapies (CAT) is organising a workshop on 15 and 16 November 2016 to discuss scientific and regulatory challenges of immunotherapy medicines based on genetically modified T-cells (white blood cells that normally fight off viruses and bacteria).


T-cell immunotherapy medicines are being developed and are currently being tested in clinical trials in a variety of cancers. However, there are still many scientific and regulatory challenges to be overcome before these innovative products can be brought to the market for the benefit of patients.



Krishan Maggon 's insight:
T-cell based immunotherapy is an innovative approach where T cells from a patient’s blood are genetically engineered in a laboratory in order to allow them to recognise cancer cells through specific receptor proteins. In the body of a patient, the modified T-cells can then identify and destroy cancer cells.
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IRAK3 is a novel innate immuno-oncology target

IRAK3 is a novel innate immuno-oncology target | Cancer Immunotherapy Review | Scoop.it
August 22, 2016 By Garrett Rhyasen, PhD Here at Oncology Discovery, we’ve elaborated on strategies to improve response rates to checkpoint inhibitors. Instead of penning another post…...

The target in question is IRAK3 (also known as IRAKM). IRAK3 has a well-established role in regulating innate immune responsiveness, mediating immune tolerance, and is a potent negative regulator of TLR/IL1R signaling. This post will attempt to elaborate on why we believe targeting IRAK3 is a differentiated, tractable, and worthwhile I/O strategy.
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Cancer & the Future: Immunotherapy

Cancer & the Future: Immunotherapy | Cancer Immunotherapy Review | Scoop.it
Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal - http://PharmaceuticalIntelligence.com

I was given a chance to participate in a new clinical trial where a protein designed new type of treatment in Immunotherapy – a new immunotherapy, called Inotuzumab. This particular drug uses antibodies that target and kill specific cancer cells. I was given the drug in the hospital where doctors monitored me for several weeks. My cancer was gone and I was able to return home where I would wait for a donor match for a stem cell or bone marrow transplant. Inotuzumab was initially designed for blood cancers and tumors, and is currently being used in clinical trials for other forms of cancer.
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CAR T-Cell Therapy The Road Ahead

CAR T-Cell Therapy The Road Ahead | Cancer Immunotherapy Review | Scoop.it
In recent years, we have witnessed a meteoric rise in clinical studies of cancer immunotherapies, catapulting immuno-oncology into one of the fastes
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Why has active immunotherapy not worked in lung cancer?Ann_Oncology

Why has active immunotherapy not worked in lung cancer?Ann_Oncology | Cancer Immunotherapy Review | Scoop.it


Why has active #immunotherapy not worked in #lungcancer?https://t.co/HwRbDsDgZS #lcsm #nsclc

Abstract Vaccines that rely on active specific stimulation of the host immune system have the potential to trigger durable antitumor responses with minimal toxicity. However, in nonsmall-cell lung cancer (NSCLC), several large phase III trials of vaccines reported within the last year have yielded disappointing results. Compared with placebo, belagenpumatucel-L (an allogenic tumor cell vaccine), tecemotide (a peptide vaccine targeting MUC-1) and melanoma-associated antigen-A3 (a protein-based vaccine) did not improve outcomes in NSCLC. The lack of clinically significant outcomes, despite their ability to prime and expand tumor antigen-specific T cells could at least partly be attributed to the inability of vaccine-induced T-cell responses to overcome the tumoral mechanisms of immune escape which limit the clonal expansion of T cells following vaccination. A number of such mechanisms have been recognized including reduced antigen presentation, antigenic loss, cytokines, immunosuppressive cells and immune checkpoints. Strategies aimed at modulating the immune checkpoints have shown promise and are on the verge of revolutionizing the therapeutic landscape of metastatic NSCLC. Overcoming immune tolerance and improving the activation of antitumor T cells via combinatorial approaches may represent a new and more promising therapeutic application for active immunotherapies in NSCLC. 

Key words active immunotherapy vaccines nonsmall-cell lung cancer immune checkpoint tumor-mediated immunosuppression 
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SITC Short Film | Society for Immunotherapy of Cancer (SITC)

SITC Short Film | Society for Immunotherapy of Cancer (SITC) | Cancer Immunotherapy Review | Scoop.it
In the early 1980’s, doctors and scientists were experimenting with a revolutionary cancer treatment known as immunotherapy. With rare cases of successful treatment, cancer patients saw their disease disappear completely. For over 30 years SITC (Society of Immunotherapy of Cancer) has been fighting for treatment and a cure for cancer through research and collaboration. SITC members all over the world are leading the charge against cancer. We’re traveling the globe to meet these thought leaders and demonstrate the crucial work that they’re doing to impact advances in both the science and clinical application of immunotherapy.
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Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. - PubMed - NCBI

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. - PubMed - NCBI | Cancer Immunotherapy Review | Scoop.it
Oncologist. 2016 Aug 17. pii: theoncologist.2016-0164. [Epub ahead of print] REVIEW

Abstract : Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) represent a new treatment paradigm in non-small cell lung cancer. Three phase III trials have demonstrated a survival benefit and improved tolerability of nivolumab and pembrolizumab when compared with standard second-line chemotherapy. Nevertheless, the adverse events associated with PD-1 inhibitors are unique; early recognition and treatment are essential. This review summarizes the required monitoring and appropriate management of immune-related adverse events in lung cancer patients receiving these agents. 

IMPLICATIONS FOR PRACTICE: The potential adverse events of immune checkpoint inhibitors differ from conventional chemotherapy and can require a multi-disciplinary approach. Continued education is important for all physicians to ensure optimal care for patients. ©AlphaMed Press. 

KEYWORDS: Immune-related adverse events; Immunotherapy; Lung cancer; Programmed cell death protein-1; Programmed death ligand-1; Toxicities
Krishan Maggon 's insight:
Oncologist. 2016 Aug 17. pii: theoncologist.2016-0164. [Epub ahead of print] 
PMID: 27534573 DOI: 10.1634/theoncologist.2016-0164
Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. 

O'Kane GM1, Labbé C1, Doherty MK1, Young K1, Albaba H1, Leighl NB2.
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Advaxix Immunotherapy Lm TECHNOLOGY

Advaxix Immunotherapy Lm TECHNOLOGY | Cancer Immunotherapy Review | Scoop.it

Advaxis’ technology uses bioengineered Listeria monocytogenes (Lm) bacteria to stimulate the immune system and target tumor cells for elimination.


Our goal at Advaxis is to fundamentally alter the way physicians and patients think about cancer by utilizing advances in genomic and molecular analysis, combined with our unique Lm Technology™, to create immunotherapies that specifically target cancer without affecting normal tissue. Our treatments enable the body to recognize tumors as threats that should be targeted by the body’s natural defenses. 

Krishan Maggon 's insight:
Learn more about Advaxis’ Lm Technology™ and its clinical and commercial partnerships. View our corporate presentation.
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Immunotherapy of Lung Cancer: An Update

Immunotherapy of Lung Cancer: An Update | Cancer Immunotherapy Review | Scoop.it
Michael P Kosty, MD, FACP, FASCO
Medical Director, Scripps Green Cancer Center gives an update on Immunotherapy of Lung Cancer
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The Strategy of Precision Editing the Cancer Cell Glycocalyx using an “antibody–enzyme conjugate” for Cancer Immunotherapy: Research Beyond “augment the activator or remove inhibitor, or both”

The Strategy of Precision Editing the Cancer Cell Glycocalyx using an “antibody–enzyme conjugate” for Cancer Immunotherapy: Research Beyond “augment the activator or remove inhibitor, or both” | Cancer Immunotherapy Review | Scoop.it
The Strategy of Precision Editing the Cancer Cell Glycocalyx using an “antibody–enzyme conjugate” for Cancer Immunotherapy: Research Beyond "augment the activator or remove inhibitor, or both" Reporter:...
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Foundation Medicine Adds New Immunotherapy Features to Product Pipeline

Foundation Medicine Adds New Immunotherapy Features to Product Pipeline | Cancer Immunotherapy Review | Scoop.it
Foundation Medicine Adds New Immunotherapy Features to Product Pipeline #immunotherapy https://t.co/4n7mHX6MKp
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Better Predict Immuotherapy Response with Tumor Mutational Burden and FoundationOne Genomic Profiling

Better Predict Immuotherapy Response with Tumor Mutational Burden and FoundationOne Genomic Profiling | Cancer Immunotherapy Review | Scoop.it
Tumor Mutational Burden (TMB) is a predictive biomarker for cancer immunotherapy. FoundationOne and FoundationOne Heme accurately measure TMB.
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Foundation Medicine adds new immunotherapy features to its gene profiling products | Pharmafile

Foundation Medicine adds new immunotherapy features to its gene profiling products | Pharmafile | Cancer Immunotherapy Review | Scoop.it
Pharmafile.com is a leading portal for the pharmaceutical industry, providing industry professionals with pharma news, jobs, events, and service company listings.
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Immunotherapy of Cancer Visualized by Live Microscopy: Seeing Is Believing

Immunotherapy of Cancer Visualized by Live Microscopy: Seeing Is Believing | Cancer Immunotherapy Review | Scoop.it
The success of immunotherapy of cancer depends on several cellular events in the tumors that can be visualized by live microscopy strategies in experimental models.
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Human Papillomavirus (HPV) Vaccines

Human Papillomavirus (HPV) Vaccines | Cancer Immunotherapy Review | Scoop.it
A fact sheet about human papillomavirus (HPV) vaccines for the prevention of infection with certain types of HPV, which is the major cause of cervical cancer.
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The virus you want to catch: Oncolytic virotherapy. ecancer - News

The virus you want to catch: Oncolytic virotherapy. ecancer - News | Cancer Immunotherapy Review | Scoop.it
The virus you want to catch: Oncolytic #virotherapy https://t.co/YcdCGWLA1C via @ecancer https://t.co/df22M9Sy31
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Immunotherapy in Community Settings: There's No Referring It Away - Institute for Clinical Immuno-Oncology

Immunotherapy in Community Settings: There's No Referring It Away - Institute for Clinical Immuno-Oncology | Cancer Immunotherapy Review | Scoop.it
As an early immuno-oncology adopter, Dr. Sigrun Hallmeyer shares her first-hand experience and how she sees immunotherapy growing as the fourth pillar of oncology in community settings.
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Fatigue or Autoimmune Disease? Physician Talks Immunotherapy Side Effects

Fatigue or Autoimmune Disease? Physician Talks Immunotherapy Side Effects | Cancer Immunotherapy Review | Scoop.it
<p>Yvonne Saenger, director of melanoma and immunotherapy at Columbia University Medical Center, discusses the side effects patients should look out for when they are on immunotherapy, and how to determine if they are experiencing normal therapy-induced fatigue or if they are suffering from a hormone reaction and should go see their medical team.</p>

<p>&nbsp;</p>
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Pioneers of Cancer Cell Therapy: Turbocharging the Immune System to Battle Cancer Cells — Success in Hematological Cancers vs. Solid Tumors

Pioneers of Cancer Cell Therapy:  Turbocharging the Immune System to Battle Cancer Cells — Success in Hematological Cancers vs. Solid Tumors | Cancer Immunotherapy Review | Scoop.it
Pioneers of Cancer Cell Therapy:  Turbocharging the Immune System to Battle Cancer Cells -- Success in Hematological Cancers vs. Solid Tumors Curator: Aviva Lev-Ari, PhD, RN Chimeric Antigen Receptor T-Cell Therapy: Players in Basic & Translational Research and Biotech/Pharma The companies are teamed with academic pioneers: Novartis with University of Pennsylvania; Kite Pharma with the National…
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Amgen licenses Advaxis Immunotherpy ADXS-NEO

Amgen licenses Advaxis Immunotherpy ADXS-NEO | Cancer Immunotherapy Review | Scoop.it
THOUSAND OAKS, Calif. and PRINCETON, N.J., Aug. 2, 2016 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and Advaxis, Inc. (NASDAQ:ADXS) today announced a global agreement for the development and commercialization of Advaxis' ADXS-NEO, a novel, preclinical investigational cancer immunotherapy treatment that is designed to activate a patient's immune system to respond against the unique mutations, or neoepitopes, contained in and identified from each individual patient's tumor. This collaboration brings together Amgen's development expertise in immuno-oncology with Advaxis' MINE™ (My Immunotherapy Neo-Epitopes) program, which is uniquely positioned to develop a customized approach to cancer treatment.

Amgen receives exclusive worldwide rights to develop and commercialize ADXS-NEO. Amgen will make an upfront payment to Advaxis of $40 million and purchase $25 million of Advaxis common stock. Amgen will be fully responsible for funding clinical and commercial activities. Advaxis will lead the clinical development of ADXS-NEO through proof-of-concept, retain manufacturing responsibilities, and receive development, regulatory and sales milestone payments of up to $475 million and potential high single digit to mid-double digit royalty payments based on worldwide sales.
Krishan Maggon 's insight:
About MINE™ (My Immunotherapy Neo-Epitopes) / ADXS-NEO MINE™ (My Immunotherapy Neo-Epitopes) and ADXS-NEO are designed to activate a patient's immune system to respond against the unique mutations, or neoepitopes, contained in each individual patient's tumor. This strategy, using massive parallel sequencing, eliminates the need for predictive algorithms and enables the development of truly personalized immunotherapies that can be manufactured in a manner that is cost-effective and timely for patients. 

 MINE™ will evaluate the immunologic and anti-tumor activity of this patient tumor-specific, neoepitope-based immunotherapy. Advaxis and Amgen will use learnings from MINE to identify and target neoepitopes using Lm Technology™ and later develop patient specific immunotherapy constructs that incorporate the neoepitope sequences identified in the patient's tumor cells. Clinical studies using ADXS-NEO are in development.
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Checkmate Pharmaceuticals

Checkmate Pharmaceuticals | Cancer Immunotherapy Review | Scoop.it
Checkmate Pharma is developing a new approach for cancer immunotherapy, by specifically activating the immune system to recognize and kill tumor cells throughout the body, without harming normal tissues.
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