Second ‘don’t eat me’ signal found on cancer cells

weissman stanford.jpg

Fascinating and important article on finding a second "don't eat me signal" that certain cancers use to protect themselves.   Article about Irving Weissman and his team's work at Stanford can be read here.

"... aggressive cancers express a ‘don’t eat me’ signal in the form of CD47 on their surfaces. Now we’ve identified a second ‘don’t eat me’ signal and its complementary receptor on macrophages. We’ve also shown that we can overcome this signal with specific antibodies and restore the ability of macrophages to kill the cancer cells.”

Irving Weissman, Stanford University School of Medicine

stanford logo.jpg

3 keys to scale-up CAR T-Cell therapy manufacturing

pa consulting.jpg

Good article on the challenges of scaling up CAR T Cell therapy manufacturing in BioProcess Online by Perry Yin from PA Consulting.  We agree with points made regarding logistics and designed the evo® Cold Chain 2.0 system to meet these new challenges.   You can read the article here.

1. Optimize the Manufacturing Process Through Automation

2. Coordinate Logistics With Real-Time Tracking And Feedback

"Given how personalized CAR T-cell therapy is, the patient is an integral component of the supply chain. It is critical that the cellular material taken and produced from one patient is only used to treat that specific patient and that the entire process is completed as quickly as possible. The logistics involved in getting the cells out of the patient to the manufacturing facility and then back into the right patient require complex logistical coordination, involving significantly higher levels of tracking than other cold-chain products that are not as patient-specific and time-sensitive."

3. Move Toward A Decentralized Manufacturing Model

 

 

evo® Smart Shipper Embedded in 8 Trials Using Treg Cells for Diabetes, Lupus, Pemphigus, and Organ Transplantation

ucsf logo.jpg

UCSF selects evo® Smart Shipper for clinical Treg Cell trials 

Critical Phase 1 research to advance treatment for autoimmune, cardiovascular, neurological diseases

Savsu Technologies is pleased to announce that our evo® Cold Chain 2.0 System has been selected for eight active and pending clinical trials at the University of California, San Francisco (UCSF) Diabetes Center and Department of Surgery. Savsu’s evo system will be used in conjunction with BioLife's hypothermic storage and cryopreservation freeze media in the important Phase 1 trials investigating effective cold chain management for the distribution of regulatory T cells known as Tregs.

The evo® Cold Chain 2.0 system was chosen in a rigorous evaluation process to determine the best method for temperature regulation and logistics visibility of high-value shipments of source material. 

Bruce McCormick, President of SAVSU, stated, "We are honored that the Diabetes Center and the Department of Surgery at UCSF have selected our evo Smart Shipper technologies. We specifically designed the evo Smart Shipper to improve cold chain logistics and transport survival of small payload cellular therapies such as Tregs."

In an announcement, Jeffrey Bluestone, Ph.D.. the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology and Director of the Hormone Research Institute in the Diabetes Center, commented, "Tregs hold great promise as treatments for autoimmune diseases such as diabetes, rheumatoid arthritis and lupus, and even as therapies for cardiovascular disease, neurological diseases and obesity. Effective cold chain management is an important potential component for commercial distribution of these novel cell-based therapies if approved."

Savsu recognizes both the importance and the special challenges of early phase trials and have designed our “evo Phase 1”program to support leading research institutions such as UCSF while significantly reducing operational risk.

For more information about our evo Phase1 program please contact us.

 

Kite Nabs First Adult CAR-T Approval

xconomy.jpg

"...remarkable recoveries from desperate cases of cancer have led to early approval..."

Really great company doing really great things.    Congrats to everyone at Kite!

We are living in remarkable times.

Read article about the approval at Xconomy here

Dude Where is My CAR-T?

biopharma reporter logo.png

Ravi Nalliah, CEO at TrakCel talks about the new era of "personalized logistics" in this article in BioPharma Reporter.

Note: see our April Blog entry about our collaboration with TrakCel here

Dude where’s my CAR-T? Personalised meds need personalised logistics, says TrakCel

By Dan Stanton+, 01-Sep-2017

After receiving approval Kymriah, Novartis must prove it can handle the supply chain complexities of manufacturing high-value and time-sensitive CAR-T cell therapies, says logistics firm TrakCel.

http://www.biopharma-reporter.com/Downstream-Processing/Novartis-must-prove-it-can-handle-complex-CAR-T-supply-chain-TrakCel

trakcel logo.jpg

BBC: Zika virus used to treat aggressive brain cancer

Getty image from BBC post

Getty image from BBC post

Fascinating article on using Zika virus to fight brain cancer.

"It looks like there's a silver lining to Zika."

"latest research shows the virus can selectively infect and kill hard-to-treat cancerous cells in adult brains....Zika injections shrank aggressive tumours in fully grown mice, yet left other brain cells unscathed."

Article posted on  BBC website (read post here), from a report in the Journal of Experimental Medicine

Nanoparticles and Gene Therapy @ The Hutch

fred hutch logo.png

Scientists seeking a simple and gentle way to provide short-term gene therapy have a new tool: nanoparticles. In a paper published August 30 in Nature Communications, Dr. Matthias Stephan at Fred Hutchinson Cancer Research Center describes nanoparticles he has developed that can streamline the delivery of bundled genetic material to specific cells.

“What we’re doing is ‘hit-and-run’ gene therapy,” a strategy in which a brief change to certain cells can have a permanent therapeutic effect, said Stephan, an immunobioengineer who led the study.

Currently, scientists pursuing gene therapy must choose either targeted approaches that permanently alter cells’ DNA, or short-term approaches that are damaging to cells and can’t be restricted to a particular cell type. Now there is a third option.

The nanoparticles’ ability to gently and temporarily provide gene-editing proteins to specific cells is “really the key” that makes the new approach stand out...

 The nanoparticles are formed by bundling synthetic messenger RNA (modified to be safer and more stable than natural RNA) into miniscule packages surrounded by a biodegradable coat. The coat itself is studded with molecules that help the nanoparticles home in on exactly the right cell type.

The researchers showed that hours after the nanoparticles are taken up by target cells, the cells begin churning out proteins based on the new messenger RNA they’ve received. Then, within days, production ceases as the messenger RNA degrades.

Read the full Fred Hutchinson Cancer Research Center article here.

Historic Day!

fda logo.jpg

 FDA announcement on approval of Kymriah CAR T therapy from Novartis.    Historic announcement:  First gene therapy to be approved in the US.  FDA announcement:  read here

"The safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent."

And from Novartis' announcement:

"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients' lives," said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine, who is a pioneer of this new treatment. 

 

Note:  my August 30 original post had a mistake in it.   I referenced a section in the FDA announcement that referred to Actemra instead of Kymriah.   I have corrected the post.

Intriguing data with Juno's new CAR-T therapy

juno logo.png

These new therapies continue to amaze...

Article here

"CAR-T developer Juno Therapeutics has reported data suggesting the benefits of this type of cancer immunotherapy could extend long after the treatment is delivered."

"...the case study 'shows the ability of anti-CD19 CAR-T cells to re-expand in vivo months after the initial CAR T-cell infusion and to re-exert antitumor activity' "

"The big question now is why the CAR-T cells re-activated. The researchers suggest that it may have been a result of the biopsy procedure itself, triggering the response when the presence of the tumour on its own was not sufficient."

Increase Control, Reduce Costs?

fisher bio logo.png

When on message boards we have all read the familiar phrase “don’t hijack this thread” which means don’t stray off topic.   With this post, I am dangerously close to doing that.  So, first let me point you to a new post and white paper offered by Simon Ellison at Fisher Bioservices called “Controlling Complexity [Not Cost] of Advanced Therapy Supply Chain”.   You can visit that page here.  Read it and digest it.   There, I have done my part…now on to the hijacking.

In reading that post, I came across three phrases which combine to support a very similar point that we have been making to decision makers about switching to our evo Cold Chain 2.0 system.  Adopting our evo system increases your CONTROL of your supply chain.  Simon makes the very important point that costs are reduced by increasing control:

…if therapy developers can reduce complexity, they can reduce cost

…complexity is driven by the fact that the therapeutic product is moving between organizations and every movement, although mitigated by SOPs, is a change of location, and personnel.

…complexity is reduced when there is control over chain of custody transactions. 

This may be a bit non-intuitive as control is usually a function of effort (labor hours and activity) which suggests that increasing control inevitably results in higher cost.   However, in the era of “always on”, connected devices this traditional assumption is wrong.   Higher control reduces costs because of the incredibly low, incremental cost of monitoring and communication when it is automated.  [note: there is no “free lunch” and the up-front cost of developing the evo technology and building the software that keeps it running was substantial but, the result is a very low incremental cost per shipment for the user].  

High control/high communication in the evo system results in the production of actionable data and lower losses.  Once configured, the evo system automatically handles communication to all important parties so, labor cost is reduced while decision making quality is increased.  evo.is delivers location data plus, alarms when packages are opened.   Using fully integrated shippers (integrated through our evo.is API) allows monitoring of courier actions throughout the trip.   All of these capabilties increase shipper control and reduce labor costs.

The evo system further increases control by eliminating dependence on remote sites because there are no buttons to push to start cooling or data recording.   evo is always on and always recording.  Outstanding autonomy allows for “3 Pier” shipments with no interim actions or recharge by remote sites.   These features increase your control and decrease costs by eliminating losses and mistakes.

evo Cold Chain 2.0 is a highly integrated SYSTEM made up of advanced technologies that combine to increase CONTROL for therapy developers and DECREASE COSTS arising from compliance, loss, and coordination.  

Fighting Tumors With Gold!

gold nano stars.png

Very interesting article about combining gold nano stars with immunotherapy.

"The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips,"

"When a tumor dies, it releases particles that trigger the immune system to attack the remnants," said Vo-Dinh. "By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding."

Read more at: https://phys.org/news/2017-08-gold-nanostars-immunotherapy-vaccinate-mice.html#jCp

Another interesting 2016 article ("Exploding nanobubbles can kill cancer cells") in Science Magazine about using gold nanoparticles:  here

As hoped, this prevented the heat from spreading to surrounding normal tissues. But the approach had an even more important effect: It caused temperatures to rise higher where there were large clusters of gold nanoparticles. This vaporized adjacent water molecules, creating tiny bubbles that quickly expand and burst, ripping apart the cancer cells. They key, Lapotko says, is that “nanoparticle clusters produce nanobubbles in cancer cells and not normal tissue.”

SAVSU in the news: "Pharma’s cold chain is going below zero"

Cellular and genetic therapies drive a ‘new paradigm’ for logistics

Very good article highlighting the challenges of moving the new cell therapies and industry's response.   Savsu, Bruce McCormick, and our DV-10 featured in the article along with folks from BioLife, TrakCel, Fisher BioServices, and Cryoport.    Thanks to Pharmaceutical Commerce for presenting such a good article and including us.

"While all of this is generating high enthusiasm in R&D circles, logistics service providers are scrambling to revise their processes to meet the new demands of these therapies. A “new paradigm” is evolving, in the words of Bruce McCormick, President of Savsu..."

http://pharmaceuticalcommerce.com/clinical-operations/pharmas-cold-chain-going-zero/

 

Way To Go! First Approved Cell and Gene Therapy for Osteoarthritis

The use of pre formulated hypothermic storage and cryogenic freeze media is becoming the cell therapy standard practice. BioLife Solutions is the scientific leader in this field. The ability to store and freeze cells to achieve maximum post thaw viability is a critical process leading to successful cell therapy commercialization. This news represents one more important step forward in bringing the advances of cell therapies into practical commercial application. Congratulations to our friends at Biolife Solutions!

FDA Briefing Document: Novartis/Tisagenlecleucel

We are NOT Doctors but, we read this very important briefing document from the FDA because our evo Cold Chain 2.0 system will be part of the manufacturing process for Car-T cells.   Very interesting that the FDA highlighted the challenges in manufacturing this new therapy.   Specifically, they mentioned the challenge of controlling process variability: "It is also critical to understand and address sources of variability seen in the individual products. This can be a challenging issue given the complex and labor-intensive manufacturing processes involved with making a CAR T cell product"

Control of process variability is one of the most important outcomes of adopting the evo Cold Chain 2.0 system.  The superior thermal performance and data reporting of our 2-8C evo's (designed specifically for the inbound leg), and our new DV -196C cryo shippers dramatically reduces process variability.

4.1.1 Control of tisagenlecleucel quality through manufacturing process controls

A major consideration for manufacturing tisagenlecleucel is the establishment of a well- controlled manufacturing process that can consistently produce high-quality CAR T cells that are safe, pure, and potent. Consistency in product quality is necessary to provide reasonable confidence that each lot (batch) of tisagenlecleucel will perform as expected at a given dose in patients.

In order to control the manufacturing process for consistency, it is necessary to thoroughly understand the manufacturing process and critical product quality attributes unique to the autologous CAR T cell products. It is also critical to understand and address sources of variability seen in the individual products. This can be a challenging issue given the complex and labor-intensive manufacturing processes involved with making a CAR T cell product (Figure 1). These challenges can include variability in the starting materials (e.g., patient’s own leukapheresis cells) and human or animal derived reagents (e.g., serum, antibodies); and control of critical components that may be manufactured under contract (e.g., transfer vectors that encode CAR, final container).

Novartis Briefing Document: Click Here

FDA Briefing Document: Click Here

Brooks Automation: Study Comparing Two Methods of Preparing, Transporting, and Storing Live T-Cells

A recent poster authored by Brooks Life Science Systems and BioLife Solutions compared two methods of preparing, transporting and storing live T-cells at both -80°C and -190°C to demonstrate best practices to achieve the highest post-thaw viability.

The quality of procedures and products used for preparing, transporting and storage of cells at both -80°C and -190°C temperatures have a direct impact on post-thaw viability and functionality. Sub-standard preparation, handling, storage, and products may subject cells to improper cryoprotectant exposure, poorly controlled shipping and storage conditions and temperatures.

Savsu participated in this study with Brooks and BioLife.  Great work.

You can download this poster instantly here: http://go.brooks.com/Preserve-T-Cells

 

Unanimous Advice To FDA: Approve Landmark CAR-T Cancer Therapy

“It’s the most exciting thing I’ve seen in my lifetime,” said Timothy Cripe, a blood cancer and bone marrow transplant specialist at Nationwide Children’s Hospital in Columbus, OH.

...The therapy would involve genetically modifying a patient’s T cells to kill cancer and then infusing them back into the body. The dramatic effect of the treatment, known for years as CTL-019, was never questioned at the meeting. Of 68 young people receiving it, 52 of them had an excellent response almost immediately, with their cancer disappearing within the first three months. Three-quarters of those patients remained cancer-free six months after treatment.

This is a really big deal for the industry.

  Read the full article here