What are the challenges of immunotherapy?

What are the challenges of immunotherapy and T cell therapy? One of the challenges of immunotherapy or T cell, especially T cell therapy for cancer is that as a result of prior treatment or as a result of long efforts to try and attack or contain the myeloma, T cells can become so-called exhausted or they don't really become tired per se, but it's a term that means that they get suppressed or down-regulated, that they're sort of turned off or switched off, and so they're not able to proliferate and expand and attack the cancer with quite the same efficiency and effectiveness as they could before. So one of the things we're learning is that it is important to utilize T cells or immune cells that are relatively fit, that are relatively able to become activated and proliferate, or we provide them with some of the signals or the wherewithal to convert to that more activated and functional state. Is it better to do immunotherapies earlier on when your T cells are healthier? I think that that's the logical progression of how these treatments will be used, that they will probably be used in earlier lines of therapy for the reasons you just mentioned, specifically that patients with more advanced disease will tend to have immune systems that are more impaired, and as a result, for instance, the CAR T cells that are being made from the cells from their blood may not be as effective or you may not be able to get as many effective cells from that type of product. So I think that once these products are approved, they will be used in earlier lines of therapy when patients' immune systems are more fit or intact and able to result in a better product, potentially. So cellular therapy and immunotherapy are really great questions because in reality we want Goldilocks, and I know this may sound silly, but the answer to almost everything in medicine and life is Goldilocks. We don't want it too hot and we don't want it too cold. So if we give a bi-specific or an immune drug or cellular therapy and it doesn't expand enough and it doesn't fight hard enough, well then the porridge is too cold, it doesn't get the job done. But if it overwhelms the immune system and activates it so, so much, you can get sick from that and that's the porridge too hot. What we want is Goldilocks. We want it just right. We want our immune system to ramp up just enough to fight off all the bad stuff, but not so much that it starts attacking our body in any ways. That's the challenges we face in the clinic and in treatment trials where if the treatment's not enough, can we find a way to augment it and if it's too much, can we find a way to bring it back down.