The Acute Myeloid Leukemia Channel on VJHemOnc is an independent medical education platform, supported with funding from BMS (Silver), and through an educational grant from Jazz Pharmaceuticals. Supporters have no influence on the production of content. The levels of sponsorship listed are reflective of the amount of funding given.
AACR 2025 | SENTI-202 reflects the trend toward logic-gated immune cell therapies in hematologic malignancies
Stephen Strickland, MD, SCRI at TriStar Bone Marrow Transplant, Nashville, TN, comments on how the development of SENTI-202 represents a broader trend toward engineered logic-gated or modular immune cell therapies in hematologic malignancies. Unlike traditional autologous CAR T-cell therapy products, SENTI-202 is an allogeneic, off-the-shelf CAR-NK therapy that can be readily available to patients without the delay of leukapheresis and cell engineering. Dr Strickland also highlights the incorporation of a “NOT” gate into this product. This unique feature prevents the attack of healthy hematopoietic cells expressing endomucin, thereby reducing myelosuppression and allowing for more effective targeting of malignant cells. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago, IL.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Obviously, in the currently available cellular therapies, whether they be for lymphoid malignancies, lymphomas, or even ALL, but also for multiple myeloma, those are all currently autologous products. And so those products, the patient has to be well enough and stable enough in order to undergo leukapheresis, the collection of cells from the patient themselves. Those cells then have to be sent off and engineered, and that process can sometimes take six weeks or so from the time of collection before the cells are engineered, ready, and available to be given back to the patient...
Obviously, in the currently available cellular therapies, whether they be for lymphoid malignancies, lymphomas, or even ALL, but also for multiple myeloma, those are all currently autologous products. And so those products, the patient has to be well enough and stable enough in order to undergo leukapheresis, the collection of cells from the patient themselves. Those cells then have to be sent off and engineered, and that process can sometimes take six weeks or so from the time of collection before the cells are engineered, ready, and available to be given back to the patient. And so as you can understand, patients with cancer, six weeks can be a long time for some malignancies, and as a result, those patients often need some other type of bridging therapy either due to disease progression or potentially toxicity of the bridging therapy. It’s also possible that those patients may not actually make it to the time point to receive the cells. And so there’s a lot of interest in trying to figure out, can we use an allogeneic product, a product that can be prepared ahead of time from a healthy donor, engineered, cryopreserved, and be quote-unquote on the shelf and ready when the patient is identified and when the patient is in need to be able to be utilized.
And so that’s one aspect that opens the door for a product like SENTI-202, which is an allogeneic product. It’s also a CAR NK-cell as opposed to what we currently have commercially available, which are CAR T-cells. So it’s a different cell type that is being utilized for this engineering process. But in addition, the other unique characteristics, we know that, as I mentioned earlier, CD33 is a validated target, and we have currently available drugs that target CD33, but one of the barriers to those agents is actually myelosuppression. The other agents that are available don’t target just the leukemic cells or just the malignant cells, they can actually target normal hematopoietic cells that also express CD33. And so in that instance, in developing this product, what they’ve also incorporated is what we call a “NOT gate”. And that is that cells that express endomucin, which is primarily expressed on healthy hematopoietic cells, when those cells express endomucin and the CAR-NK senses that, it actually turns the CAR-NK off, if you will, or prevents the attack of that healthy hematopoietic cell, even if that cell is expressing CD33 or possibly FLT3. So it’s sort of a smart system, if you will, in the sense that it doesn’t just see, attack, destroy every cell that has those markers, but it really is primed to hopefully focus its attacking capability on the malignant cells.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
