Benjamin McLeod’s Post

Cellares has gained a lot of attention since they launched the Cell Shuttle last year. Regardless of what you think of them, this news is a very impressive accomplishment. A $380M reservation fee has to be some kind of record 😅 https://lnkd.in/gCFr-zAx #celltherapy #innovation #biotechnology

Promising companies have died this way. You could join them if you’re not careful. Here are 5 ways to avoid that: 1. Facility Compliance Should Be Default Design your layout such that: - Cleanliness is prioritized - Contamination risk is minimized 2. Quality Management from Day 1 - It has to be robust - It has to have strong documentation - Audits and quality checks are frequent 3. Qualified Supplier Networks - Be rigorous - Ensure the quality of consumables - Make sure all suppliers meet GMP 4. Stay Ahead of the Regulatory Curve - Don’t be caught by surprise - Company policies should reflect where the ball is going - not where it is right now 5. Data Integrity is King - You need impeccable records - Traceability should be second nature - It’ll take a lot of stress out of regulatory inspections So remember… Company success depends on getting GMP right. Strong, innovative companies have crashed and burned because they ignored this. Learn from their mistakes. Succeed where they failed. Any thoughts on this? Drop them in the comments. #biotechnology #gmp #cellandgenetherapy #regulatory

The ASGCT program is finally out! Now for the hard part: What sessions to attend? If you’ve got any suggestions, let me know in the comments. (Also, keep your eye out my top poster and talk recommendations - forthcoming the closer we get to the event). Hope to see you there! American Society of Gene & Cell Therapy #cellandgenetherapy #biotechnology #innovation #genetherapy #celltherapy

What's inside an AAV? Let's break it down. There are four major components: 1. The Promoter - Landing pad of transcription factors to express the transgene 2. The Transgene - Therapeutic payload to help the patient 3. Woodchuck Hepatitis Virus (WHP) Posttranscriptional Regulatory Element (WPRE) + PolyA tail - Regulatory elements that aid transgene expression - However, since WPRE has viral origin, it's being phased out 4. Inverted Terminal Repeats (ITRs) - Flanks on either side of the sequence - Hairpin structure - Assist in both packaging and expression of transgene Hope this helps! NOTE: there are other, small components of the AAV genome (LoxP sites, for example), but for the sake of simplicity, those other components haven't been included in this diagram. Want other bite-sized pieces of content that explain the science of cell and gene therapy? Check out #cgt_simplified #biotechnology #genetherapy #aav #viralvector #science #cellandgenetherapy

AAV costs are high, and purity is low. But this paper finds a way to address that. And it's so simple that anyone can use it. The Problem: - Most people use triple transfection for AAV production - While flexible, all that plasmid DNA is an impurity risk - Plasmids are also very expensive - This method also struggles with complex therapeutic genes, reducing yields The Solution: Standard techniques use a 1:1:1 ratio of the plasmids. Instead, the authors propose substantially reducing the amount of the plasmid carrying the transgene (the cis-plasmid) while keeping the amounts of other two plasmids constant. As in, a 10-100x reduction in the cis-plasmid. The Results: - Improved production yield of challenging genes by up to 10 times compared to normal - Significantly decreased the encapsidation of unwanted plasmid DNA, (from 4.4% down to as low as 0.7%) - Demonstrated that rAAVs produced with this method have comparable or superior effectiveness in delivering gene therapies in vivo, with significantly fewer undesirable DNA and RNA contaminants from the plasmid in tissue Folks, this is rare. A solution that anyone can implement. Reducing an expensive component doesn't usually increase quality. But this time? It absolutely does. A welcome change. Kudos to the authors Hao Liu, Yue Zhang, Mitchell Yip, Lingzhi Ren, Jialing Liang, Xiupeng Chen, Nan Liu, ailing du, Jiaming Wang, Hao Chang, Hyejin Oh, Chen Zhou, Ruxiao Xing, Mengyao Xu, Peiyi Guo, Dominic J. Gessler, M.D., Ph.D., Jun Xie, Phillip Tai, Guangping Gao and Dan Wang - excellent work! For more papers on viral vector process development, check out #pdjournalclub #genetherapy #biotechnology #innovation #aav

To all the NK, TIL, M, γδT and NKT pioneers... CAR-T is ahead for now, but don't worry. Your time will come! #celltherapy #innovation #cancer #science #fdaapproval

CAR-T therapies have a problem: Historically, they've only been approved as last-line (or very late-stage) treatments. A recent FDA announcement is starting to change that.

Immune reactions to AAV are a big problem. But fixing the capsid & transgene isn't enough. There's another culprit. Nucleic acid contaminants. What are they? - Consistent sequences that show up in purified preps - You can have re-existing immunity for them - Includes mutated and truncated genomes - But also junk from replication and host cells What the authors did: 1. Developed a model nucleic acid "antigen" to study the effects it would have when co-administered with a hepatic AAV gene therapy 2. Used quantitative analysis to measure changes in: - Liver enzyme levels - Circulating therapeutic protein levels - T-cell responses both the contaminant and AAV capsid 3. Examined T-cell responses and correlated them with biochemical markers of liver injury and therapeutic protein levels The Key Results: 1. The contaminant decreased gene therapy efficacy and increased liver enzyme levels. 2. The immune responses targeting contaminant-derived antigens can lead to the clearance of transduced hepatocytes. - Basically, cells that actually get the therapy are targeted and destroyed 3. The authors have set up a new mouse model to study this effect further. Don't sleep on contaminants, folks. Make sure you've optimized your process to minimize them. Kudos to the authors Mark Brimble, Christopher Morton, Stephen Winston, Isaiah Reeves, Yunyu Spence, Pei-Hsin Cheng, Junfang Zhou, Amit Nathwani, Paul Thomas, Aisha Hegab Souquette, PhD and Andrew Davidoff - great work! For more papers like this, check out #pdjournalclub #genetherapy #aav #innovation #biotechnology #research

How have Chimeric Antigen Receptors gotten better? Here's an overview of the big improvements: 1st Generation: - Only contained a CD3 signalling domain 2nd Generation: - Now a co-stimulatory domain is added - Further pronounced effect 3rd Generation: - What's better than one co-stimulatory domain? - Two! 4th Generation: - Co-stimulatory domains only get you so far - These CARs also express chemokines like IL-2 5th Generation: - On top of everything so far... - Special co-stimulatory domains that activate important pathways like JAK/STAT3 These CARs will only get better and better... Who knows what the 15th generation will be like. Kudos to Mohsen Sheykhhasan et al for this insightful figure. For more posts like this, check out #cgt_simplified #celltherapy #cartcelltherapy #biotechnology #cancer