BSH 2024 | The development of iNKT-CAR T-cells for hematological malignancies

So the recent days, I can clearly see that the CAR-T immunotherapy is very promising for blood cancer treatment. So we are based in Multiple Myeloma Center Langmuir Myeloma Center, based in Imperial College London, which is headed by Professor Karadimitris.

We are working on many different diseases like leukemia and lymphoma, but we are mainly focused on curing multiple myeloma. So we set several strategies and plans to cure multiple myeloma. One of our main strategies using the iNKT immune cells, that’s the invariant natural killer T-cells, which is very rare in our peripheral blood. Since it’s very rare, we are taking these cells out of the peripheral blood from a healthy donor, we engineered the cells using lentiviral particles, and we express the CAR (chimeric antigen receptor), which is going to bind to an antigen which is expressed on multiple myeloma. We are mainly focused on using BCMA. This is one of the highly expressed antigens expressed on the cell surface of the multiple myeloma. So we have developed an antibody against BCMA where we take this and express an iNKT immune cells and then will be just taking them into the clinical trials. So today here I’m going to talk about, one of the mechanisms, how we really optimize the strategy, how we optimize our platform. So we have several different costimulatory molecules, which is part of a CAR –  so CD28, 41BB, OX40, so we have used these three different costimulatory molecules, and combining together we make second generation CAR and third generation CAR. So how this costimulatory molecule is really playing a key role, and which is the best for using our platform to go for a highly efficient treatment strategy. So here, not just about that, but we also developed bispecific antibodies against multiple myeloma. One arm is going to target the multiple myeloma, the other arm is going to target the iNKT cells. So basically, we will give maximum amount of iNKT cells and also the antibodies. Multiple myeloma is one of the incurable blood cancers, so we are thrilled by combining so many different molecules and strategies to cure multiple myeloma. Not just with that, but I also would like to add one of the key points is that we have a commercial partner. They are aimed to go for the clinical trials using the CAR-iNKT platform, they are expanding our platform to treat lymphoma. So they are set to start early next year. So today it’s all about iNKT immunotherapy and how good they are and how we really optimize the system and go for efficient treatment.