In the thymus we trust: Protcellular therapy and the future of allogeneic immunotherapy

In the thymus we trust: Protcellular therapy and the future of allogeneic immunotherapy

Insightsfrom industryOlivier NegreChief Scientific OfficerSmart immuneIn this interview, News Medical speaks with Olivier Negre, Chief Scientific Officer at Smart Immune, about revolutionizing his seminar at the 7th Annual Allogeneic Cell Therapies Summit later this year.

Can you please introduce yourself and tell us a little about your research and professional background?

Hello, I am Olivier Negre, Chief Scientific Officer at Smart Immune since 2020. I now have over 20 years of experience in biotherapy and gene therapy. My journey started working on recombinant vaccines at Bioprotein Technologies. In 2000, I joined Bluebird Bio, where I worked for 14 years to develop the first approved gene therapy for beta thalassemia.

Throughout my career, I have moved from a senior scientist in France to director of translational research in the USA. I then returned to France to found Biotherapy Partners and led the Smart Immune Protcell platform as Chief Scientific Officer. I am also a board member of the French Society of Gene and Cell Therapy.

They will present a seminar at the 7th Annual Allogeneic Cell Therapy Summit later this year. Can you give us a little insight into what you will discuss during your conversation?

I look forward to introducing the recent advances of our Protcell therapy and more specifically our efforts to deliver effective and diverse T-cell receptors (TCR) while ensuring safety. Our research has shown that our allogeneic T cell progenitors, once formed in the host thymus, reconstitute a polyclonal T cell compartment. TCR diversity is crucial for fighting infections and eliminating cancer cells that express neoantigens.

What are some key findings from your preclinical studies on the safety of Protcells?

Without spoiling the presentation, I can say that we have not observed any product-related toxicity such as GVHD. A protective effect against tumor challenge was observed in our preclinical models.

Why is the thymus an important factor in this therapy and how does this affect T cell development?

Our cell therapy Smart101 (T cell precursors derived from allogeneic blood stem cells) is intended to be strengthened and personalized by the patient's thymus. The thymus selects and establishes immature T cells, transforming only the best candidates into fully functional naïve T cells and ready to defend the body against malignant and infected cells. Interestingly, the thymus naturally expands Protcell-derived T cell populations by approximately 1,000-fold. We like to say this in the thymus we trust!

What are the potential medical applications of prot cells and what makes them particularly promising?

There are numerous reasons why our approach can address the medical needs associated with T cell dysfunction. Our strategy is to use allogeneic prot cells and exploit thymus formation to restore the immune system with a new, competent and long-lasting T cell force. It has great potential for applications in post-transplant hematology as we now work in high-risk acute leukemia, but also in other cancers, immune aging and infectious diseases such as AIDS. We are working to genetically engineer our Protcells to generate long-lasting, self-tolerant and targeted therapies such as HIV-resistant T cells or CAR Protcells.

Why have we seen headwinds in the allogeneic cell therapy space in recent years?

The field faces obstacles that tend to be partially and gradually resolved: safety, long-term efficacy (VS cell creation), rejection, and manufacturing complexity. Smart Immune is one of the players in the space that aims to solve all these hurdles to provide off-the-shelf and accessible T-cell therapies.

What are the most exciting advances you see in the allogeneic field of allogeneic cell therapies that are transforming the field?

An increasing number of cellular immunotherapies are reaching the market (CAR-T, TCR-T, TILs), but they are largely autologous and face several limitations, e.g.

The allogeneic approach can circumvent these limitations and is made feasible through several improvements:

1) New gene editing methods that reduce the risk of off-target effect and genomic instability

2) The development of IPS cell lines for the practically unlimited amount of starting material

3) The sophisticated selection of donor cells

4) epigenetic and metabolic considerations

5) Using T cell precursors to maintain the TCR while avoiding GVHD

Where do you see the allogeneic cell therapy space in the next 5 years?

The approval of Ebvallo, the first authorized allogeneic T-cell immunotherapy, paved the way for new products. The Poseida therapeutics showed that allogeneic CAR-T therapies can have strong traction for pharma, with the deal acquired by Roche Holdings for $1.5 billion. In the coming years, the field of cellular immunotherapy should mature, and large-scale production of high-quality, affordable products should enable frontline treatment of more patients. Cell banking allogeneic off-the-shelf products should participate in this new cell therapy space.

What are you most looking forward to at the 7th Annual Allogeneic Cell Therapies Summit?

The Annual Allogeneic Cell Therapy Summit is the place to meet with experts in the field and learn about the latest advances in allogeneic therapies. I look forward to joining the industry leaders' fireside chat to discuss how to achieve allogeneic product success by aligning innovation with investor expectations. The panel discussion scheduled for the second day will be particularly interesting as ensuring durable therapeutic responses for allogeneic therapies is challenging. I will be interested in discussing strategic patient selection through HLA matching.

Download the 7th Allogeneic Cell Therapies Summit Event Handbook

What are the next steps for you and your research? Do you have any exciting projects?

I will be able to share more about the development of our Protcell programs during the conference. Our focus in the coming months will be on CAR prot cell engineering and experiments to support future clinical trials in solid tumors.

Where can readers find more information?

• Die Website von Smart Immune
• Folgen Sie Smart Immun auf LinkedIn
• Weitere Informationen zum 7. allogenen Zelltherapiengipfel

About Olivier

Olivier earned a degree in Biotechnology from ENSTBB and a PhD in Cell and Molecular Biology from Diderot University in Paris. He has been working in the field of biotherapies for more than 20 years, including the production of recombinant proteins using bioprotein technologies and gene therapy programs at Bluebird Bio in both France and the USA. Olivier is a board member of the French Society of Genes and Cell Therapy, co-president of the think tank Gene and Cell Therapy Institute, co-founder of Biotherapy Partners and currently CSO at Smart Immune.

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