The New eXosome Files: ISCT 2024 Features 3 Abstracts from RoosterBio on Bioproduction of Extracellular Vesicles

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Vancouver, CA

  • RoosterBio will be showcasing at Booth #244 for ISCT this year in Vancouver. We are also to present three pioneering abstracts and will engage in an ISCT Scientific Signature Series panel session, with a focus on advancements in the upstream and downstream bioproduction of extracellular vesicles (EVs).
  • RoosterBio Founder, Jon Rowley, PhD, will also be chairing a Concurrent Session, titled “Entering the MSC 2.0 Era: MSCs as Cellular Building Blocks for Next Generation Therapies” introducing three exciting speakers from SHIFTBIO (Gi-Hoon Nam, MD, PhD), EpiBone (Sarindr “Ik” Bhumiratana, PhD), and Cytonus Therapeutics (Remo Moomiaie-Qajar, MD), as well as a featured in a panel session, “Transitioning MSC-EV Manufacturing from Basic Research to Clinical Applications.”
  • The meeting in Vancouver is anticipated to be a hub for innovative advanced therapies and regenerative medicine development, with RoosterBio as a depot for enhancing MSC 2.0 applications and EV harvesting processes.
  • Interested to learn how a parallel between “The X-Files” and the dynamic, complex field of applied biological research nod to potential revelations about EVs and MSCs at the conference? Read on!

Did You Hear The Rumors?

The characters of Fox Mulder and Dr. Dana Scully were once seen about town in Vancouver and may return for a special cold case to solve at the end of May 2024. Unconfirmed reports indicate that a new chapter in their saga of intrigue and mystery may be imminent, to be called “The eXosome Files.” Naturally, it will explore the great cosmic enigma of extracellular vesicles (EVs).

At past ISCT annual meetings, 1, 2, 3, 4, 5 we witnessed that these biological particles began to mysteriously pop up with increasing regularity, in abstracts, in presentations—even in pub conversations! Now EVs are everywhere! But where did they come from? And what might be their ultimate purpose for humans on this planet? Perhaps “the truth is out there…”

As regular attendees of past ISCT (International Society for Cell and Gene Therapy) meetings, RoosterBio is happy to inform you that we’ll most certainly be presenting three new abstracts at this year’s event, scheduled from May 29 to June 1 at the Vancouver Convention Center. And while we neither confirm nor deny the existence of 🥸 “extra-CELL-estial vessel calls” 🥸 emanating from this conference’s logistical planning, we do profess to eagerly rekindling welcome conversations with old friends, colleagues, and partners. What can all of us expect to find? First, we hope for a lot of viewers to interface with our posters, titled here:

  • A Fed-Batch Chemically Defined hMSC-EV Bioprocess Medium Enabling 2-4x EV Yield Improvements in Bioreactor Culture | Authored by Terri Willstaedt, Amy Walde, Jon A. Rowley
  • A comparability study of chromatography resins suitable for EV purification from a highly productive MSC Bioprocessing Platform | Authored by Jae Jung, Stephen Lenzini, Michael Budiman, Jon A. Rowley, Elie Zakhem
  • Scalable GMP-compatible Process Solution for MSC-EV Purification with 10X Yield Improvements | Authored by Stephen Lenzini, Jae Jung, Madeline Cramer, Elie Zakhem, Jon A. Rowley

“A Fed-Batch Chemically Defined hMSC-EV Bioprocess Medium Enabling 2-4x EV Yield Improvements in Bioreactor Culture,” exhibits a novel, chemically defined, scalable fed-batch bioreactor production medium that enables a streamlined production of hMSC-EVs, potentially increasing EV yield by 2-4 times and simplifying the process by removing the need for a medium exchange. It was validated across multiple MSC donors and tissues of origin and shown in a scaled-up proof of concept via a 3L stirred tank. This chemically defined bioreactor medium is formulated to minimize non-EV residual material in collected cell secretome material, all while keeping the producer cells in optimal health.

“A comparability study of chromatography resins suitable for EV purification from a highly productive MSC Bioprocessing Platform” depicts RoosterBio’s recent ongoing collaboration work with Cytiva, where we compared the integration of two chromatography resins (Capto Core 400 and SuperSEC) into our multi-operation downstream process (DSP) for purification of extracellular vesicles out of MSC-conditioned medium. It will be reported here that both resins showed similar high extracellular vesicle recovery and increase in purity, a clear indication that most of the impurities were cleared through those resins. We’ve recently noted how SEC holds promise as a later-stage unit of operation in DSP for EV preparation. SEC is proving to be a pivotal process step to enable extracellular vesicle purification without harsh elution conditions.

“Scalable GMP-compatible Process Solution for MSC-EV Purification with 10X Yield Improvements” introduces a novel, drop-in reagent named Agent V, which significantly increases the yield of MSC-EVs during downstream processing. With Agent V, the yield improved tenfold while maintaining EV critical quality attributes. Additionally, we evaluated the CD73 activity of treated extracellular vesicles and showed that it was maintained as a plausible readout for biological function in the post-DSP samples. We cannot overestimate how significant this new product is going to be for many of our current and future partners when combined with our other complementary bioprocesses.

In addition to three posters, RoosterBio Founder and Chief Product Officer Jon Rowley, PhD, will be featured in a panel session (6/1/24, 12:30-13:45) titled “Transitioning MSC-EV Manufacturing from Basic Research to Clinical Applications,” together with Professor Sai Kiang Lim of A*STAR and Nisa Renault, PhD of Fujifilm Cellular Dynamics, Inc. As part of the ISCT Signature Series, MSC-EVs: Paving the Road to Regulatory Approval, a main learning goal will be to augment early awareness of key manufacturing parameters for seamless integration between a process development unit’s pre-clinical MSC-EV preparations and the manufacturing team’s ultimate cGMP clinical product.

Rowley will also be on stage to introduce the concept of “MSC 2.0” with three outstanding session speakers via SHIFTBIO (Gi-Hoon Nam, MD, PhD), EpiBone (Sarindr “Ik” Bhumiratana, PhD), and Cytonus Therapeutics (Remo Moomiaie-Qajar, MD). MSC 2.0 as a concept is beginning to groundswell due to MSCs’ industrialized supply chain and democratized accessibility as a cell manufacturing technology. Specifically, MSCs have reached an inflection point where they can now be considered as routine manufacturing starting materials—and where the final product is no longer merely a simple cell suspension for infusion. Each of these companies will be describing medical technologies that might well have sounded like science fiction to Agents Scully and Mulder only 20 years ago. We eagerly look forward to providing you with a synopsis of these proceedings in a forthcoming blog!

Taken together, RoosterBio’s ISCT 2024 posters and delegation will feature our recent diligent efforts to radically improve industrial bioprocess to expand MSCs and harvest highly pure and bioactive extracellular vesicles from them. These titles immediately hint that RoosterBio’s been busy, particularly in the extracellular vesicle/exosome bioprocess space from both the upstream and downstream ends. Our progress has been non-trivial and made big leaps recently, and we’ll be gladly entertaining many questions on how we and our partners made it all possible.

To paraphrase Mark Twain, history doesn’t exactly repeat, but it often rhymes. By looking back at last year’s ISCT documentation and the cell and gene therapy (CGT) news stream—and surveying the environs of 2024’s event—we can surmise how it will play out. Despite a few speed bumps in 2023, it’s fair to speculate that research into mesenchymal stem/stromal cells (MSCs) will continue to generate lots of buzz this May. Alongside (and often within) the reported CAR-Ts, iPSCs, HSCs, gene editing, immunotherapy, and process development activities, these cells appeared on more than one-third of ISCT 2023’s abstract titles. 1 Moreover, as “MSC 2.0” therapeutic concepts begin shifting into high gear, 6 many researchers and developers are looking to MSCs as an enabling biomaterial for engineered tissues, 7, 8, target=”_blank” rel=”noopener”9, 10 ex vivo gene therapies, 11, 12 isolated mitochondria, 13, 14, 15, 16, 17, 18 and artificially targeted extracellular vesicles 19 or hybrid EV-LNPs. A case-in-point: ISCT 2023 saw more than two-thirds of the EV-related abstract titles referencing MSCs as a key producer cell type.

word-cloud-ISCT-2023

Image, above (openai.com) depicts a word cloud formed from 693 abstract titles featured at 2023’s Annual ISCT Meeting in Paris, France

One fruitful area of collaboration in cell therapy explores how different cell types can play well together. As the home to Aspect Biosystems, STEMCELL Technologies, Notch Therapeutics, and other thriving biotechs, Vancouver is no stranger to practical expertise in complex cell biology. Accordingly, we might expect some attending this meeting to be thirsty for new spinoffs of CAR-T, beyond oncology, applied towards conditions like heart disease, fibrosis, senescent cells and aging, or infectious disease.

Another angle is where adjunctive cell types could show synergies. For example, teams at the University of British Columbia and BC Children’s are highly regarded as pioneers who adapt CAR targeted therapy toward autoimmune conditions via Tregs (in lieu of CTLs) as the active cell ingredients. 20, 21, 22 In parallel, we and others note that off-the-shelf MSCs could help polarize and/or “educate” co-cultured cell type phenotypes (e.g., Tregs) during their ex vivo processing or after infusion to enable a more potent therapeutic effect. 23, 24 Allogeneic MSCs not only modulate Tregs in human physiology and ex vivo, but also have been used to facilitate rapid advance into a clinical trial employing anti-fibrotic tissue-remodeling monocytes. 25 MSCs could also potentially perform in an immuno-oncology “tag team” with CAR-T when coaxed to differentiate into powerful antigen-presenting cells (APCs). 26

X-Files Dall-E Generated Image

Image by Dall-E

“Nothing happens in contradiction to nature, only in contradiction to what we know of it. And that’s a place to start. That’s where the hope is…” was insightfully stated by Dana Scully, MD, in a noted X-Files episode.

Looking into 2024, RoosterBio expects that the advanced CGTs discussed at ISCT’s annual meeting will likewise be cause for hope…under not-too-dissimilar circumstances from Agent Scully’s. That is, much like the misty, non-linear, bottomless warren of the X-Files’ mythos, applied biological research is highly complex, context-dependent, and subject to dynamic inputs and outputs. This makes the quest for cures inspired by…and made from…biology a struggle. However, in nature, contradictions cancel themselves out of existence, leaving only what is true and knowable and, quite possibly, engineerable. RoosterBio will be on-site in Vancouver to engage with our fellow community. Together, we seek deeper understanding, where the truth is not only “out there,” but “among us.”

 

References
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  2. RoosterBio RoosterBio Joins the Action at ISCT, ASGCT, & ISEV in May 2022. https://www.roosterbio.com/blog/roosterbio-joins-the-action-at-isct-asgct-isev-in-may-2022/.
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