CAR T-cell therapy: another step forward in cancer treatment?

CAR T-cell therapy: another step forward in cancer treatment?

Hello everybody,

This week has started from another great news in the world of cancer research!

The scientists from Dr. Riddell’s lab at the Fred Hutchinson Cancer Research Center (Seattle) have demonstrated that engineered T- cells (which normally act to destroy cancer cells) after being re-introduced to people with the Acute Lymphoblastic Leukemia (ALL) (blood cancer) caused a complete remission in more than 90% of terminally ill patients. Moreover, the response rate was 80% and no signs of tumor cells was in more than 50% of patients suffering from other blood cancers (Non-Hodgkin’s Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)).

The method used is called CAR T-cell immunotherapy which can be divided into three big steps (Figure 1):

  1. Individual’s T- cells are extracted;
  2. In a lab, T-cells are modified (by adding a synthetic molecule- chimeric antigen receptor (CAR), specific for patient’s tumor cells);
  3. Engineered T-cells are introduced back to the patient.

Then patients are monitored for a disease response, for instance, by CT scans. The presence and the number of T-cells is also evaluated by performing biochemical analysis, such as RT-PCR.

CAR-Engineered_T-Cell_Adoptive_Transfer

Figure 1: The method of CAR T-cell immunotherapy. The picture taken from: https://en.wikipedia.org/wiki/Chimeric_antigen_receptor#/media/File:CAR-Engineered_T-Cell_Adoptive_Transfer.jpg 

You can find a video from the lab and the story of discovery at: https://www.fredhutch.org/en/news/center-news/2016/02/immunotherapy-remission-blood-cancer-AAAS-riddell.html  

CONS against the therapy

Although this is a very promising treatment option against the ALL and some other types of blood cancers, experts in the field believe that people put too many hopes to this treatment option.

For instance, Cai Xuan a pharma analyst from Global Data believes that the price for this type of therapy ($300,000-$500,000) is higher than for  the existing stem cell transplantation  ($100,000-200,000) . Therefore, more studies should be done to prove the advantages of the emerging type of the treatment (from: http://pharmatimes.com/Article/16-02-18/T-cell_hype_ignoring_cost_and_safety_concerns_say_experts.aspx).

Dr. Alan Worsley from Cancer Research UK in the interview to BBC confirmed that “…although this is exciting, it is still the first step“. The reasons are as usual: price, expertise and time.  Biomedical scientists are needed, who are the experts in immuno-oncology. Although this is a growing field, some time is needed to “get” such people, so that this method can be widely used. Also, the technique itself requires a significant amount of time, so that cells can grow in a lab. For more information: http://www.bbc.co.uk/news/health-35586834 

Another aspect we need to put attention to is the safety of a technique. As Dr.Worsley says: “This is especially important, as for instance, in chemotherapy, as soon as the drug is not administered, the treatment is finished”. However, here is a different mechanism of action: as soon as the cells are infused back to the patient, “they go and live”. Therefore,  we need to ensure that “they go after THE right (cancerous) cells… targeting THE right things”.

There are treatment options available (e.g.: chemotherapy, oncovin or doxorubicin) to cure the ALL; however, these have unpleasant side- effects, such as hair loss. As for majority of the drugs, during the clinical trials of CAR T-cell immunotherapy unfortunately, people also developed  adverse reactions, such as very low blood pressure or  neurological syndrome. However, Dr. Riddell believes that these can be overcome by reducing the number of T-cells  infused back to the patient.

Finally, Dr. Worsley  mentions that normally, in the ALL condition chemotherapeutics are given and these are effective in 70-70% of cases. However, in the described clinical trial, the treatment was used in patients, who developed resistance to other drugs.  Now the questions remain, whether it can be used as a first-line therapy or applied to different cancers.

Dr. Riddell’s group has initiated clinical trials for some type of breast, lung and pancreatic cancers, sarcoma and melanoma.  However, only the time will show, whether this will be an effective form of the treatment in these cases.

Although this is a very exciting and promising news, some experts believe that currently we are too far away from the time, when CAR T-cell immunotherapy will be used as a regular treatment option.

Nevertheless, the amount of research and clinical trials in immunotherapy has significantly increased in the last years and hopefully, in the near future the technique of re-engineering T cells could be optimized and become a treatment option not just for blood cancer(s), but also for other types of malignancies.

Finally, there always were and would be those, who are in favor of conservative methods of treatment (such as chemotherapy). However, without trying to improve and/or optimize new medicinal options, we would not be able to make a step forward. Therefore, I believe, although we might be not quite there (yet) to make CAR T-cell immunotherapy as a form of a first-line treatment, this IS a big step forward in the field of immuno-oncology and hopefully, one day this will stand in a line with chemo- and radiotherapies.

Thank you very much for your time! I hope, you found this post interesting and as always, I wish you a LOT of HEALTH !!! 

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Figure: T-cells surrounding cancer cell. Taken from: flickr.com

 

Another advancement in Breast Cancer research.

Another advancement in Breast Cancer research.

Hello everybody,

Today is a great day! Another great day for the Breast Cancer Research! 

The scientists from the University of Manchester have identified a protein EPHA2, which contributes to the breast cancer progression.

Let me bring a short introduction on the disease and it’s progression. Breast cancer can be local and/or become metastatic (spread of cells from the origin to a distant site, like bone or brain). It is subdivided into four stages (Figure 1), each of which is determined by the combination of Tumor size (T), lymph Node status (N) and Metastasis (M) (called the TNM system).

More information on the breast cancer stages can be found:  http://ww5.komen.org/BreastCancer/StagingofBreastCancer.html

 

Breast-Cancer-Stages2

Figure 1. Breast cancer development and progression. From: fda.gov

Breast cancer becomes metastatic when it reaches Stage IV. Here, cancerous cells leave their original site (breast tissue), break into the bloodstream, migrate and enter the new site (e.g.: bone) (Figure 2).

6Figure 2: Migration of cancer cells. From: news.leiden.edu/news-2015/genes-discovered-that-have-effect-on-spread-of-breast-cancer.html

Today the researches have identified that when tumor cells are in the blood vessels and interact with the walls, these regulate EPHA2 protein. When EPHA2 is active, the cancerous cells remain inside the vessels; however, switching off EPHA2 (by a biochemical modification, called phosphorylation) allows cancer cells to leave the blood vessel and move to a new site.

The full article on the discovery: http://stke.sciencemag.org/content/9/414/ra15 

The lead researcher, Claus Jorgensen concluded: “The next step is to figure out how to keep this receptor switched on, so that the tumor cells can’t leave the blood vessels – stopping breast cancer spreading and making the disease easier to treat successfully” (from: http://www.business-standard.com/article/news-ians/how-breast-cancer-cells-spread-from-blood-vessels-116021001209_1.html )

This is a great news in the world of cancer research!  Identification of markers like EPHA2, is a step towards finding solution to stop the disease progression. More research should be done. However, every step counts and hopefully, in the future EPHA2 could become a drug target for metastatic breast cancer and it’s regulation save thousands (or millions) of lives!

Thank you very much for your time and as always, I wish you a LOT of HEALTH!

The life before and after breast cancer diagnosis.

The life before and after breast cancer diagnosis.

Hello Everybody,

Today I would like to share a story, which really fascinated and inspired me. That night I could not sleep… I woke up at 3 a.m. and started writing a blog about Jo Taylor, a breast cancer survivor… and I believe, stories like hers cannot be left unnoticed.

A night before I have attended a cancer conference, where Jo shared her story of the disease and how her life changed after breast cancer diagnosis.

Jo was diagnosed with breast cancer when she was 38, married, having two very young children…As for every patient, such a diagnosis is a great shock! Nevertheless, Jo maintained and even empowered her active lifestyle: she is jogging, cycling and practicing yoga. Moreover, Jo rode a bike from Manchester to Blackpool (60 mile), while being on a chemotherapy treatment (Abraxane, Perjeta and Herceptin). Finally, she has created the “After Breast Cancer Diagnosis” web-site: http://www.abcdiagnosis.co.uk/, which provides additional information on the available treatments, surgeries and just supports women who faced the same problem as the author did.

You can read Jo’s full story at: http://www.abcdiagnosis.co.uk/index.php/about-me/2013-02-13-04-18-53

JT

After a very inspiring talk at the conference, I had a chance to ask Jo questions about the life before and after breast cancer diagnosis.

Is there a family history of breast cancer?

No, no one in the family had ever had breast cancer.

At what stage you were initially diagnosed with breast cancer and how it was detected (e.g.: BSE, mammogram)?

I had found a lump by chance and went to my GP the next day.  Mammogram and ultrasound with core biopsy confirmed.

How did you select a doctor and the surgery? This is a crucial for the treatment; can you give an advice of how to choose “wisely”?

My surgeon was chosen due to knowing someone who had the operation I wanted to have and she was at a hospital in the Manchester area.  Seeing another patient’s good surgery was how I choose, but also knowing their credentials and experience in OncoPlastic surgery for breast cancer was also a key.

Did the doctor provide you with the information on the available treatment options or did he offer you what he believed is the most suitable for you? Was this information enough for you to make a decision or you had to do additional research?

The original Surgeon didn’t, but the one I choose did. I did the research mainly and he followed it up with what he offered.

Can you explain the treatment process in greater details? Did you have serious side effects caused by medicines?

I had a full mastectomy with all node clearance from under the arm.  I had a Latissimus Dorsi muscle taken out of my back and placed still attached into the breast cavity.  Due to not having enough muscle I had a small implant as well.  After that I had: chemotherapy, radiotherapy, Herceptin and Zolodex, all with side effect. Chemo of course is a very toxic so yes, serious side effect with that in particular.

Was there any psychological help and support provided by NHS/ medical institution to accelerate the treatment process?

Sadly none offered, but had this further down the line.

You have always been a very active person: jogging, cycling and yoga are part of your life.  Have your lifestyle changed since the diagnosis?

Not really, I think I have become even more active!  I do have limitations so have to adapt with any issues I have.

Is there a collaboration between the patients and clinicians AND patients and pharma companies to tackle the disease? In case there is, how does it work? If not, do you believe anybody will benefit from such a network? 

Haha! In a word no, they have a job to do and don’t want to waste their time talking to patients, but charities have patient voices where they can possibly advocate making changes. Lack of statistics, especially for secondary breast cancer is a real problem therefore we cannot create change or push pharma if we don’t have solid figures.

What could be the challenges of creating such a “team”?

The normal problems would arise, time, resources, money…

Have you been or thought of collaborating with SMEs (e.g.: medical communications) or bigger pharma companies to promote the disease awareness in the population? Do you believe sharing patients’ stories of overcoming/ coping with the disease could help people to better understand breast cancer and increase knowledge on the available treatment options?

I am involved with Salford University to share my own cancer story to nurses that are training.  Unfortunately I do not have the time or resource to think about collaborations but I do have my own web site which people can freely access which provides knowledge and treatment options.

You are the founder of “After breast cancer diagnosis” web-site http://www.abcdiagnosis.co.uk/ which aims to support women by providing information on the treatment choice, available breast cancer surgeries and getting advice from those who went through it. You also give some tips on a diet and exercise. Are you doing it on your own or you have a support group? Can people join the team?

I do this on my own via social media, twitter and Facebook page.  Anyone can chat or join into anything. I don’t have a forum, but hope people are motivated and possibly inspired by what I do.

The “after breast cancer” web-site is very comprehensive and now you plan to make an app. Do you want to include additional features to it?

Only a better way of having reconstruction photos on there with a search engine but a web based app so nothing stand alone.

What advice will you give to people recently diagnosed with breast cancer?

Live your life, enjoy and get out exercising to see the benefits it will have with your recovery physically as well as mentally.

Can people get in touch with you and if so, what is the best method to approach?

Connect with me on Twitter, Facebook or email info@abcdiagnosis.co.uk

Although I am an oncology scientist, unfortunately, I had never had a chance to meet or work with cancer patients. Is it a lack of education system or is it a way our society works? I believe the reason lies in the latter : everybody does what they were told to do without willing to go an extra mile?

This interview clearly confirmed the idea that there is a growing division between the patients, doctors and pharma companies… As we are all aiming to save and improve patients’ lives, advance diagnosis and help people to live longer, we need to establish a dialogue between these three groups of people as then, the biomedical scientists will get the feedback, how the treatments work, what are the drawbacks and what innovations are needed, while healthcare practitioners will get a deeper understanding of developing medicines and new treatment options.

Jo Taylor is a first patient, I have interviewed and I believe more people need to speak about their stories… as these are as different as us. Hopefully, this will help to cease the partition in the (medical and healthcare) society. After all, we have a single aim

           to BEAT CANCER!

Thank you very much for your time and as always, I wish you a lot of HEALTH!

P.S. I would be grateful if you would like to share YOUR story, and will contact me: kargina.anastassia@gmail.com

Let’s beat it!

Let’s beat it!

Today, the 4th of February is the World Cancer Day!

The aim of the day is to promote cancer awareness, so that less people get the diseasemore research is made and thus, more people are cured; and the quality of life of those who undergo the treatment is improved!

This year’s the tagline: “WE CAN. I CAN“, meaning that YOU can take the action to help to tackle the calamity!

How can YOU and US TOGETHER do it?

WE CAN by: preventing cancer, promoting active and healthy lifestyle, increasing the awareness of the relationship between the everydays’ habits and cancer risk factors, support and further improve education of medical specialists, collaborate and communicate…

I CAN by:  taking preference to have an active and healthy lifestyle, be aware that early cancer diagnosis can save a life, ask for and provide support, share the story and express your opinion and vision…

…and many-many more, which you can find on the “World cancer day 2016” official web-site at: http://www.worldcancerday.org/about/2016-2018-world-cancer-day-campaign 

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Cancer affects everyone and TOGETHER we can take the action to reduce the impact it has on our community and thus, to BEAT cancer sooner!

And don’t forget, you can show your support and help to beat cancer, too! From promoting campaigns on social media, translating educative material or  participating in the events. Find out more at: http://www.worldcancerday.org/get-involved 

Drug discovery and development.

Drug discovery and development.

Hello everybody,

I would like to start my blog by writing a more optimistic post and discuss how the new drugs are discovered and developed.

Often, when I meet people and introduce myself as a research oncology scientist, they ask me: Why does it take “them” so long to discover new medicines and why are these so expensive? I will try to answer these questions and explain in a simple way,  why is it such a costly and long-term process.

Successful drugs take at least ten years from conception to clinic, costing upwards of $2.6 billion. The exception is a newly approved drug Tagrisso– it took around seven years, only 2.5 of which- for clinical trials. It is prescribed to people diagnosed with a specific form of non-small cell lung cancer. For more information: https://www.astrazeneca.com/our-company/media-centre/press-releases/2015/TAGRISSO-AZD9291-approved-by-the-US-FDA-for-patients-with-EGFR-T790M-mutation-positive-metastatic-non-small-cell-lung-cancer-13112015.html .

Unfortunately, there is a high attrition rate (drug failure) which causes around 90% of the drugs to fail after the first clinical trials. Drug safety tests have a great impact on drug development leading to drug withdrawals. Therefore, to avoid highly expensive late-stage failures (the later stage is, the more expensive it is), toxicology assays have been developed to identify drugs that are highly probable to fail at the early stages (“fail-early” strategy).

Therefore, the high cost of a newly developed medicine can be explained by the high attrition rate caused by the approval of only a few medicines out of the thousands and sometimes millions of compounds that have been tested during the early Research and Development (R&D).

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So, why drug development is such a long process?

This is because the whole process is divided into FIVE broad stages: basic research, drug discovery, drug development, FDA review and Clinical Use (Figure 1).

The pipeline of drug development

Figure 1: The pipeline of drug development. Adapted from: Hughes, et.al., 2011.

Below I will shortly introduce you to each of these elements. However, more information and in- depth review on drug discovery and development can be found at: http://www.fastbleep.com/biology-notes/37/114/636 

Drug discovery. 

During the initial stages of drug development or  basic research potential molecules (such as proteins) that are involved in disease are identified. It is a challenging process because these are involved in a variety of biological processes by being members of cellular pathways (so called links between the molecules).

Consequently, modification of certain pathways may have extreme toxic effects and be unsuitable for further drug development. Moreover, to become a good drug target (a molecule in the body, which upon interaction with a potential drug produces an effect, e.g.: prevents disease development), the molecule should be “druggable”, for instance, be a small molecule and express a biological effect upon its binding. Finally, it should be safe, efficacious and pass clinical and commercial requirements. The tests are done on cells, tissues and animal models to determine, whether potential medicine will influence the molecule.

the-impact-of-early-adme-profiling-on-drug-discovery-and-development-strategy

After the target is selected, during the drug discovery phase, the researchers try to narrow the library of compounds from thousands to a single lead compound, which in the future can become a potential medicine. A variety of approaches can be used, such as high-throughput screening (selects the most promising molecules out of thousands), genetically-engineered living systems that target the molecule of interest or creating a molecule from a living/ synthetic material.

Early safety tests of the promising compounds take place before the use in humans. At this stage, promising compounds are tested for pharmacokinetics (how the body processes the compound) and pharmacodynamics (the impact of a potential drug on the body systems and functions). Such tests are done in cells, animals or computational systems.  To become a successful drug, it must meet certain criteria: be Absorbed into the bloodstream, Distributed to the site of action, Metabolized efficiently, Excreted from the body and exert no toxic effects (ADME pharmacology testing).

In the next stage (Lead optimization) potential drugs are altered or “optimized” in their chemical structure to improve their properties. For instance, by reducing interaction with other proteins within the pathway, the potential side effects can be minimized.
When one or more compounds are identified, pre-clinical testing determines, whether these are safe to be used in humans. The studies in the living cells and animal models determine the drug’s mechanism of action and the potential adverse effects. At this stage, the way of producing large quantities of drugs to be used in clinical trials should be also established.

Drug development. Clinical trials. 

Pre-clinical research should exclude most potentially toxic compounds; however, it is important to determine any unexpected side effects with the human body. Prior to the clinical study, the aims of the research for each of the different phases are set up (Table 1) and the investigational new drug process (IND) begins. The IND application includes the data from in vivo and toxicity studies, manufacturing information and the study plans.

Table1

Table 1: Phases of clinical trials, highlighting: the number of participants involved, the aim and the focus of the research. Adapted from: (Pharma.org)

Regulations and Approval: FDA Review.

The Food and Drug Administration (FDA) regulatory review evaluates the complete data sets and proposes the labeling and manufacturing plans. Upon the positive confirmation of safety and efficacy results from the clinical trials, a new drug application (NDA) is submitted (where results from pre-clinical, clinical development programs, proposals for manufacturing and labeling are considered) to get approval for drug marketing.

Drug approval is a very long and thorough process and occasionally, additional screens and tests are requested to prove the novel drug has an advantage over the marketed drug.

Manufacturing: high quality production of new medicines on a large scale. 

The approved drugs can be administered to a small population of patients or to millions of people. In either case, during each stage of the manufacturing procedure, quality and safety checks are conducted to ensure that companies meet good manufacturing practice (GMP) requirements approved by FDA. During manufacturing, the cutting edge technologies are implemented (i.e.: nanotechnology) which are closely coordinated with the automation and software.

drug-manufacturing

Post-approval research and monitoring.

Upon completion of R&D work the drug research continues and monitors its efficacy and new long-term side-effects. Moreover, it can be repositioned to a new patient population. Additional beneficial properties of a drug can be revealed leading to expansion of its use. For instance, the drug’s therapeutic value is maximised when for a given indication it has a greater therapeutic value than seen during clinical trials, it can be used to target a different disease, has a new way of delivery or brings an advantageous effect when used as a combination therapy.

To summarize, drug development is a very long and complex process, sometimes taking up to 10-15 years to develop a new medicine. Increased understanding in human biology and disease biochemistry opens the doors for new advances in drug discovery and possibilities to discover a new treatment option. Considering the advances in research and medical innovations, there is a hope that  the success of drug development will improve in the near future.

I hope, this post helps to understand why is it such a long and expensive process to develop a single drug.

Thank you for your time.

I wish  ALL the readers a lot of HEALTH and a BRIGHT FUTURE!!! 

Anastacia

P.S. As usually, your comments are highly welcome!

Introduction

Introduction

Hello everybody,

Let me introduce myself: My name is Anastacia and I am a passionate young oncology scientist, who wants to make the life of millions of people better! Much better!

You will ask “how“? The answer is- to support public by improving the understanding about healthcare and increasing the awareness about different diseases, especially cancer. Every year, around 14 million of people in the World are diagnosed with such a disease. And this is the reason why we keep researching and developing new medicines and thankfully, the number of approved anti-cancer drugs increases year by year!

The number of oncological indications for which the drug was approved at the initial indication and later as a supplement medicine. To summarize, between 1949 and mid-2015 oncology drugs were approved for almost 300 indications! (Available at: http://www.managedcaremag.com/archives/2015/10/fda-approval-oncology-drug-indications-1949-2015). 

To decrease the number of patients, who are diagnosed with the disease at the late stages, we need to significantly improve the AWARENESS about it. And this is the first reason why did I start to write this blog.

Also, there is a big gap in collaboration between the patients, clinicians and pharma companies, not saying about the “miscommunication” between the patients and the industries. And this is the second reason: I would like to share the vision from either sites and try to improve communication within the community. Thus, I will be happy if you will share your stories, propose the topics for discussion and GET INVOLVED!

In the future posts I will describe and explain different cancer types (causes, available treatment options) and speak with cancer survivors who had overcome the disease or those, whose relatives are still affected by it.

Here, I will also discuss medical and scientific news, the latest trends in innovation and technology as well as recent updates from the Pharma World.

Finally, as I am a big book fan, especially on the topic of psychology and personal development, I think, it will be upsetting to leave authors’ great ideas unnoticed. Therefore, I plan to share their thoughts with you and hopefully, you will find them useful and interesting.

I hope, the future posts would be interesting and helpful to you!

And to finish this post, I want to wish  ALL the readers a lot of HEALTH and a BRIGHT FUTURE!!! and remember: 

inspirational-quotes-you-were-given-this-life

 

Thanks,

Anastacia