Please can you introduce yourself and tell us a little bit about your research and professional background?
Hi, I’m 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 began working on recombinant vaccines at Bioprotein Technologies. In 2000, I joined bluebird bio, where I worked for 14 years on the development of the first approved gene therapy for beta-thalassemia.
Throughout my career, I've transitioned from a Senior Scientist in France to Director of Translational Research in the USA. I then returned to France to found Biotherapy Partners and lead Smart Immune’s ProTcell platform preclinical development as Chief Scientific Officer. I am also a board member of the French Society of Gene and Cell Therapy.
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You will be presenting a seminar at the 7th Annual Allogeneic Cell Therapies Summit later this year. Can you give us a sneak peek at what you’ll be discussing during your talk?
I’m looking forward to introducing our ProTcell therapy platform’s recent advances and, more precisely, our efforts to maintain effective and diverse T-cell receptors (TCR) while ensuring safety. Our research has shown that our allogeneic T-cell progenitors, once educated in the host thymus, restore a polyclonal T-cell compartment. TCR diversity is critical to fighting infections and eliminating cancer cells expressing neoantigens.
What are some key insights 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 has been observed in our preclinical models.
Why is the thymus an important factor in this therapy, and how does it impact T-cell development?
Our cell therapy SMART101 (allogeneic blood stem cell-derived T-cell progenitors) is designed to be empowered and personalized by the patient’s thymus. The thymus selects and educates immature T-cells, turning only the best candidates into fully functional naive T-cells, 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 that in the thymus we trust!
What are the potential medical applications of ProTcells, and what makes them particularly promising?
There are numerous reasons why our approach can address medical needs related to T-cell dysfunction. Our strategy is to use allogeneic ProTcells and harness thymic education to restore the immune system with a new, competent, and long-lasting T-cell force. It has huge potential for applications in hematology post-transplant, as we are doing now in high-risk acute leukemia, but also in other cancers, immune aging, and infectious diseases like AIDS. We are working to genetically engineer our ProTcells, to generate long-lasting, self-tolerant, and targeted therapies like HIV-resistant T-cells or CAR ProTcells.
Why have we been seeing headwinds in the allogeneic cell therapies space for the past several years?
The field is faced with obstacles that are tending to be resolved partly and progressively: safety, long-term efficacy (vs cell exhaustion), rejection, and manufacturing complexity. Smart Immune is one of the players in the field aiming at solving all these hurdles to offer off-the-shelf, accessible T-cell therapies.
What are the most exciting advancements you’re seeing in the allogeneic cell therapies space that are turning the field around?
An increasing number of cellular immunotherapies is reaching the market (CAR-T, TCR-T, TILs) but they are mostly autologous and are facing several limitations such as the need to manufacture a batch for each patient, the complexity of a circular supply chain, the cost per dose and the poor quality of patient cells when harvested after several rounds of chemotherapy ...
The allogeneic approach can circumvent those limitations and is made more feasible by several improvements:
1) New methods of gene editing reducing the risk of off-target effect and genomic instability
2) The development of iPS cell lines for the virtually illimited amount of starting material
3) The refined selection of donor cells
4) Epigenetic and metabolic considerations
5) The use of T-cell progenitors 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. Poseida Therapeutics showed that allogeneic CAR-T therapies can have strong traction for pharma with the agreement to be acquired by Roche Holdings for $1.5 billion. In the coming years, the field of cellular immunotherapy should become mature, and large-scale production of high-quality, affordable products should allow the treatment of more patients in the first line. Cell banks of allogeneic off-the-shelf products should participate in this new area for cellular therapies.
What are you looking forward to most at the 7th Annual Allogeneic Cell Therapies Summit?
The Annual Allogeneic Cell Therapies summit is the place to be to meet with experts in the field and learn about the most recent advances in allogeneic therapies. I am looking forward to attending the industry leaders’ fireside chat, which will 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 since ensuring long-lasting therapeutic responses is challenging for allogeneic therapies. I will be keen to discuss strategic patient selection by HLA matching.
What are the next steps for you and your research? Do you have any exciting projects coming up?
I will be able to say more about the evolution of our ProTcell programs during the conference. Our focus in the coming months will be the engineering of CAR ProTcells and the experiments supporting future clinical trials in solid tumors.
Where can readers find more information?
About Olivier
Olivier earned an engineering degree in biotechnology from ENSTBB and a PhD in cell and molecular biology from Paris Diderot University. He has been working for more than 20 years in the field of biotherapies including the production of recombinant proteins with BioProtein Technologies and gene therapy programs at bluebird bio both in France and in the USA. Olivier is a board member of the French Society of Gene and Cell Therapy, co-president of the think tank Gene & Cell Therapy Institute, co-founder of Biotherapy Partners and currently CSO at Smart Immune.