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Posts Tagged ‘immuno-oncology therapeutics’


Yet another Success Story: Machine Learning to predict immunotherapy response

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Immune-checkpoint blockers (ICBs) immunotherapy appears promising for various cancer types, offering a durable therapeutic advantage. Only a number of cases with cancer respond to this therapy. Biomarkers are required to adequately predict the responses of patients. This article evaluates this issue utilizing a system method to characterize the immune response of the anti-tumor based on the entire tumor environment. Researchers build mechanical biomarkers and cancer-specific response models using interpretable machine learning that predict the response of patients to ICB.

The lymphatic and immunological systems help the body defend itself by combating. The immune system functions as the body’s own personal police force, hunting down and eliminating pathogenic baddies.

According to Federica Eduati, Department of Biomedical Engineering at TU/e, “The immune system of the body is quite adept at detecting abnormally behaving cells. Cells that potentially grow into tumors or cancer in the future are included in this category. Once identified, the immune system attacks and destroys the cells.”

Immunotherapy and machine learning are combining to assist the immune system solve one of its most vexing problems: detecting hidden tumorous cells in the human body.

It is the fundamental responsibility of our immune system to identify and remove alien invaders like bacteria or viruses, but also to identify risks within the body, such as cancer. However, cancer cells have sophisticated ways of escaping death by shutting off immune cells. Immunotherapy can reverse the process, but not for all patients and types of cancer. To unravel the mystery, Eindhoven University of Technology researchers used machine learning. They developed a model to predict whether immunotherapy will be effective for a patient using a simple trick. Even better, the model outperforms conventional clinical approaches.

The outcomes of this research are published on 30th June, 2021 in the journal Patterns in an article entitled “Interpretable systems biomarkers predict response to immune-checkpoint inhibitors”.

The Study

  • Characterization of the tumor microenvironment from RNAseq and prior knowledge
  • Multi-task machine-learning models for predicting antitumor immune responses
  • Identification of cancer-type-specific, interpretable biomarkers of immune responses
  • EaSIeR is a tool to predict biomarker-based immunotherapy response from RNA-seq

“Tumor also contains multiple types of immune and fibroblast cells which can play a role in favor of or anti-tumor, and communicates among themselves,” said Oscar Lapuente-Santana, a researcher doctoral student in the computational biology group. “We had to learn how complicated regulatory mechanisms in the micro-environment of the tumor affect the ICB response. We have used RNA sequencing datasets to depict numerous components of the Tumor Microenvironment (TME) in a high-level illustration.”

Using computational algorithms and datasets from previous clinical patient care, the researchers investigated the TME.

Eduati explained

While RNA-sequencing databases are publically available, information on which patients responded to ICB therapy is only available for a limited group of patients and cancer types. So, to tackle the data problem, we used a trick.

All 100 models learned in the randomized cross-validation were included in the EaSIeR tool. For each validation dataset, we used the corresponding cancer-type-specific model: SKCM for the melanoma Gide, Auslander, Riaz, and Liu cohorts; STAD for the gastric cancer Kim cohort; BLCA for the bladder cancer Mariathasan cohort; and GBM for the glioblastoma Cloughesy cohort. To make predictions for each job, the average of the 100 cancer-type-specific models was employed. The predictions of each dataset’s cancer-type-specific models were also compared to models generated for the remaining 17 cancer types.

From the same datasets, the researchers selected several surrogate immunological responses to be used as a measure of ICB effectiveness.

Lapuente-Santana stated

One of the most difficult aspects of our job was properly training the machine learning models. We were able to fix this by looking at alternative immune responses during the training process.

Some of the researchers employed the machine learning approach given in the paper to participate in the “Anti-PD1 Response Prediction DREAM Challenge.”

DREAM is an organization that carries out crowd-based tasks with biomedical algorithms. “We were the first to compete in one of the sub-challenges under the name cSysImmunoOnco team,” Eduati remarks.

The researchers noted,

We applied machine learning to seek for connections between the obtained system-based attributes and the immune response, estimated using 14 predictors (proxies) derived from previous publications. We treated these proxies as individual tasks to be predicted by our machine learning models, and we employed multi-task learning algorithms to jointly learn all tasks.

The researchers discovered that their machine learning model surpasses biomarkers that are already utilized in clinical settings to evaluate ICB therapies.

But why are Eduati, Lapuente-Santana, and their colleagues using mathematical models to tackle a medical treatment problem? Is this going to take the place of the doctor?

Eduati explains

Mathematical models can provide an overview of the interconnection between individual molecules and cells and at the same time predicting a particular patient’s tumor behavior. This implies that immunotherapy with ICB can be personalized in a patient’s clinical setting. The models can aid physicians with their decisions about optimum therapy, it is vital to note that they will not replace them.

Furthermore, the model aids in determining which biological mechanisms are relevant for the biological response.

The researchers noted

Another advantage of our concept is that it does not need a dataset with known patient responses to immunotherapy for model training.

Further testing is required before these findings may be implemented in clinical settings.

Main Source:

Lapuente-Santana, Ó., van Genderen, M., Hilbers, P. A., Finotello, F., & Eduati, F. (2021). Interpretable systems biomarkers predict response to immune-checkpoint inhibitorsPatterns, 100293. https://www.cell.com/patterns/pdfExtended/S2666-3899(21)00126-4

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Inhibitory CD161 receptor recognized as a potential immunotherapy target in glioma-infiltrating T cells by single-cell analysis

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/02/20/inhibitory-cd161-receptor-identified-in-glioma-infiltrating-t-cells-by-single-cell-analysis-2/

Immunotherapy may help in glioblastoma survival

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

https://pharmaceuticalintelligence.com/2019/03/16/immunotherapy-may-help-in-glioblastoma-survival/

Deep Learning for In-silico Drug Discovery and Drug Repurposing: Artificial Intelligence to search for molecules boosting response rates in Cancer Immunotherapy: Insilico Medicine @John Hopkins University

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/17/deep-learning-for-in-silico-drug-discovery-and-drug-repurposing-artificial-intelligence-to-search-for-molecules-boosting-response-rates-in-cancer-immunotherapy-insilico-medicine-john-hopkins-univer/

Machine Learning (ML) in cancer prognosis prediction helps the researcher to identify multiple known as well as candidate cancer diver genes

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/05/04/machine-learning-ml-in-cancer-prognosis-prediction-helps-the-researcher-to-identify-multiple-known-as-well-as-candidate-cancer-diver-genes/

AI System Used to Detect Lung Cancer

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2019/06/28/ai-system-used-to-detect-lung-cancer/

Cancer detection and therapeutics

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/05/02/cancer-detection-and-therapeutics/

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https://pharmaceuticalintelligence.com/biomed-e-books/

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Electronic Proceedings for 10th US-India BioPharma & Healthcare Summit, June 2, 2016, Marriott Cambridge, MA

 

Curator: Aviva Lev-Ari, PhD, RN

 

LIVE — 9AM-noon US-India BioPharma & Healthcare Summit, June 2, 2016, Marriott Cambridge, MA

https://pharmaceuticalintelligence.com/2016/06/02/live-9am-noon-us-india-biopharma-healthcare-summit-june-2-2016-marriott-cambridge-ma/

 

LIVE 11:45AM – 2:40PM US-India BioPharma & Healthcare Summit, June 2, 2016, Marriott Cambridge, MA

https://pharmaceuticalintelligence.com/2016/06/02/1145am-240pm-us-india-biopharma-healthcare-summit-june-2-2016-marriott-cambridge-ma/

 

LIVE 3:15PM – 5:00PM US-India BioPharma & Healthcare Summit, June 2, 2016, Marriott Cambridge, MA

https://pharmaceuticalintelligence.com/2016/06/02/315pm-500pm-us-india-biopharma-healthcare-summit-june-2-2016-marriott-cambridge-ma/

 

 

 

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Avvinity will have exclusive rights in oncology to use Alphamer therapeutic platform, invented by a Nobel Laureate and developed by Centauri: A Case of a Joint Venture Model, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

Avvinity will have exclusive rights in oncology to use Alphamer therapeutic platform, invented by a Nobel Laureate and developed by Centauri: A Case of a Joint Venture Model

Reporter: Aviva Lev-Ari, PhD, RN

 

 

Horizon Discovery Group plc Enters Immuno-Oncology Therapeutic Development and Forms Joint Venture with Centauri Therapeutics Limited

·           Newly formed company Avvinity Therapeutics will be jointly managed by Horizon, via its Research Biotech business, and Centauri

·           Joint venture creates a differentiated new player in the rapidly growing immuno-oncology market, currently valued at £25 billion

·           Avvinity will have exclusive rights in oncology to use Alphamer therapeutic platform, invented by a Nobel Laureate and developed by Centauri

·           Horizon to invest up to £5.3 million, with an initial outlay of £2.5 million, in a  joint venture to identify novel immuno-oncology therapeutics

·           Horizon will contribute its gene editing technology platform and oncology expertise and will also benefit from service revenues from the joint venture

·           Formation of the joint venture represents a strategic move by Horizon to capture the upside potential of its IP, platform technologies and capabilities in immuno-oncology, synthetic lethality and cell therapy based therapeutics

 

Horizon will host a conference call today at 09:30 GMT to discuss this news. To access the live conference call please use the dial-in details below. The presentation will be made available shortly before the call at:https://www.horizondiscovery.com/about-us/investor-relations/corporate-videos-and-presentations.

 

Cambridge, UK, 2 March 2016: Horizon Discovery Group plc (LSE: HZD) (“Horizon” or “the Company”), the leading international gene editing company, announces today that it has formed an immuno-oncology joint venture, Avvinity Therapeutics (“Avvinity”), with Centauri Therapeutics Limited (“Centauri”), a UK-based biotechnology company focused on the discovery and development of novel molecules targeting life-threatening infectious diseases. This transaction represents part of Horizon’s previously outlined strategy to invest up to £10 million, further leveraged by its IP, technology platforms and know-how, to identify the next generation of molecular and cellular cancer therapeutics. 

 

Avvinity will combine Horizon’s gene editing, immunology, oncology and drug discovery capabilities with Centauri’s Alphamer technology to provide a powerful and proprietary platform to discover and develop novel immuno-oncology therapeutics, for both solid tumours and leukaemias. Avvinity will be targeting an immuno-oncology market currently worth £25 billion per year and expected to grow to approximately £50 billion per year by 2020.(1)

 

Under the terms of this agreement, Horizon will out-license certain background intellectual property relating to its translational genomics and drug discovery platforms, and will invest up to £5.3 million over two tranches with the first tranche of £2.5m committed, and the second to be committed at Horizon’s discretion pending the progress of three development programs. Centauri will license background IP and expertise on its Alphamer technology to Avvinity, which will have exclusivity for the field of oncology for an initial three year period and can be extended via the issue of further equity concurrently with the raise of new investment.

 

Avvinity will be managed jointly by Horizon and Centauri, and based on the investment of IP, technology and the first tranche of funding; Horizon will own 33% of Avvinity’s equity, representing 50% of the most-preferred class of voting shares. Upon completion of the 2nd tranche of funding Horizon will own 49.99% of Avvinity’s equity, representing 50% of the most-preferred class of voting shares. The joint venture will be managed within Horizon as part of the Company’s Research Biotech business (formerly Horizon’s Leveraged business unit).

 

Neither Horizon nor Centauri will be obliged to provide further funding to Avvinity, though both retain pre-emption rights and may elect to participate in future funding rounds. Subject to achieving key development milestones, Avvinity plans to raise significant new external investment to take its innovative drugs into clinical trials, at which time the value of Horizon’s stake in the business would be highly-material.

 

Dr. Darrin M. Disley, Chief Executive Officer, President Research Biotech of Horizon Discovery Group plc, said: By combining Horizon’s deep understanding of the genetic basis of cancer alongside its gene editing, drug discovery and emerging immuno-oncology toolbox, with Centauri’s unique Alphamer technology and knowledge of its use, we have created an exciting new company to spearhead Horizon’s move into targeted therapeutic development.  We are confident this joint venture will break new ground in the development of immunotherapies, and bring significant value creation to Horizon shareholders.

 

“The establishment of Avvinity is in line with our hybrid Research Biotech strategy to not only work with partners but also take advantage of the therapeutic upside potential of the most exciting new areas of personalised and genomic medicine in a risk-managed way.”

 

Dr. Mike Westby, Chief Executive Officer of Centauri Therapeutics Limited, commented: Alphamers are an entirely novel way to target disease and represent an exciting new approach for recruitment of host immunity. At Centauri we have invested to build the Alphamer platform and assembled the drug discovery expertise necessary to exploit the platform in infectious diseases. Through this joint venture with Horizon, we look forward to applying our combined know-how and capabilities to develop Alphamers as important new immuno-oncology medicines, particularly for cancer indications that have proven intractable to date.”

 

More information on Avvinity can be found at www.avvinity.com.

 

 ENDS

 

Notes for Editors:

 

Alphamer technology is based on chemically synthesized molecules that redirect naturally occurring antibodies in the human immune system to selected pathogens or cancer cells. One end of a molecule binds a cell-surface target on a pathogen or cancer cell using an aptamer, while the other end presents specific epitopes that attach to the circulating antibodies. The result of this redirection is cell death and subsequent recruitment of the T-Cell mediated pathways to clear the body of the pathogen or cancer cell.

 

Alphamers promise key advantages over conventional antibody and antibody-drug conjugate molecules in immuno-oncology applications, including the ability to target cancers driven by both wild type (“normal”) gene overexpression as well as mutant (”abnormal”) gene overexpression, and by exhibiting a short half-life in the body yielding reduced toxicity and systemic side-effects.  Considerable investment has been made in the Alphamer technology over the past four years and its ability to engage the immune system to destroy bacteria has been confirmed.(2)

 

Platform technologies based around alternative immuno-oncology approaches have secured high valuations once early positive results in clinical trials have been achieved: Amgen’s 2012 acquisition of Micromet valued Micromet at $1.16b, and in 2013, Spirogen was acquired by AstraZeneca for up to $440m.

 

References:

1. http://www.prnewswire.com/news-releases/global–usa-cancer-immunotherapy-market-analysis-2015—forecasts-to-2020-300157219.html

 

2. Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer. Kristian SA, Hwang JH, Hall B, Leire E, Iacomini J, Old R, Galili U, Roberts C, Mullis KB, Westby M, Nizet V. J Mol Med (Berl). 2015 Jun;93(6):619-31

 

Conference call:

A conference call for analysts, investors and media will take place at 09:30 GMT today hosted by Darrin Disley, Chief Executive Officer and President, Research Biotech, and Richard Vellacott, Chief Financial Officer, who will run through a presentation followed by a Q&A session. The presentation will be made available shortly before the call at: https://www.horizondiscovery.com/about-us/investor-relations/corporate-videos-and-presentations.

 

The dial-in numbers for the conference call are:

 

UK: 08006940257

Standard International: +44 (0) 1452 555566

Conference call ID: 62637628

 

A replay of the call is available approximately four hours after the call concludes. For those unable to attend it live, or who would like to listen to it again, call +44 (0)1452550000 and quote the conference call ID: 62637628.

 

For further information, please contact:

 

Horizon Discovery Group plc

Dr. Darrin Disley CEO / Richard Vellacott CFO

Tel: +44 (0) 1223 655580

 

Centauri Therapeutics Limited

Dr. Mike Westby CEO

Tel +44 (0) 1304 728611

 

Zyme Communications (Trade and Regional Media)

Katie Odgaard

Tel: +44 (0)7787 502 947

Email: katie.odgaard@zymecommunications.com

 

Consilium Strategic Communications (Financial Media and Investor Relations)

Amber Fennell / Jessica Hodgson / Matthew Neal / Laura Thornton

Tel: +44 (0) 20 3709 5701

Email: horizon@consilium-comms.com

 

Panmure Gordon & Co. (NOMAD)

Corporate Finance: Freddy Crossley / Duncan Monteith / Fabien Holler

Broking: Tom Salvesen

Tel: +44 20 7886 2500

 

 

About Horizon Discovery Group plc www.horizondiscovery.com/

Horizon is a leading international gene-editing company that supplies products, services and research programmes that enable genomics research and the development of personalised and genomic medicines. Horizon has a diverse and global customer base of over 1,400 unique organisations across more than 50 countries, including major pharmaceutical, biotechnology and diagnostic companies as well as leading academic research centres. The Group supplies its products and services into multiple markets, estimated to total in excess of £29 billion in 2015.

 

Horizon’s core capabilities are built around its proprietary translational genomics platform, a highly precise and flexible suite of gene editing tools (rAAV, ZFN and CRISPR) able to alter almost any gene sequence in human or mammalian cell-lines.

 

Horizon offers over 23,000 catalogue products, almost all of which are based on the application of gene editing to generate in vitro and in-vivo models that accurately model the disease-causing genetic anomalies found in diseases like cancer. These ‘patients-in-a-test-tube’ are being used by customers to: understand the genetic drivers of disease; identify targets of therapeutic intervention that can moderate or correct these genetic drivers; develop novel medicines and companion diagnostic tests that result in the right patient getting the right medicine.

 

Horizon also provides custom in vitro and in vivo disease model generation services, biopharmaceutical manufacturing cell lines and generation services, quantitative molecular reference standards and contract research and custom screening services.

 

In addition, Horizon through its Research Biotech business deploys the Company’s intellectual property, gene-editing platform, products, services and know-how in cancer research, drug discovery and immunology to develop its immuno-oncology, synthetic lethality and cell therapy platforms which aim to deliver novel drug treatments into the pharmaceutical pipeline.

 

Horizon is headquartered in Cambridge, UK, and is listed on the London Stock Exchange’s AIM market under the ticker “HZD”. For further information please visit: www.horizondiscovery.com.

 

 

About Centauri Therapeutics Ltd www.centauritherapeutics.com

Centauri Therapeutics is a UK-based biotechnology company focused on the discovery and development of novel molecules targeting life threatening diseases.

 

Centauri Therapeutics has established a core R&D facility at Discovery Park in Sandwich, Kent, with an experienced team of industry scientists focused on discovery, optimisation and development of novel Alphamers targeting acute hospital acquired infections. The company is currently focussed on the development of Alphamers against anti-microbial resistant (AMR) pathogens, which pose an increasing threat to human health.

 

Centauri Therapeutics’ Executive team is led by Mike Westby, Chief Executive Officer (previously Pfizer, Roche) and Stuart Lawson, Chief Financial Officer (CEO of the private investment group Animatrix Capital LLP, and previously KPMG). Clive Dix is Non-Executive Director and Chairman of the Board (previously Convergence Pharmaceuticals, PowderMed, PowderJect, Glaxo Wellcome).

 

SOURCE

From: “Katie Odgaard” <katie.odgaard@zymecommunications.com>

Date: March 2, 2016 at 2:12:41 AM EST

To:avivalev-ari@alum.berkeley.edu” <avivalev-ari@alum.berkeley.edu>

Subject: Horizon Discovery Group plc Enters Immuno-Oncology Therapeutic Development and Forms Joint Venture with Centauri Therapeutics Limited

Reply-To: katie.odgaard@zymecommunications.com

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