WEBVTT 00:03.461 --> 00:06.464 - CAR-T cells are a relatively new treatment 00:06.464 --> 00:09.175 that's FDA approved for cancers. 00:09.175 --> 00:12.887 So this is a treatment where normal immune cells are modified 00:12.887 --> 00:16.599 so that they can identify and kill cancer cells. 00:17.642 --> 00:21.730 - Amongst the many, many types of cells that are part of the immune system, 00:21.771 --> 00:23.231 one type are called T cells. 00:23.231 --> 00:27.610 One of the things that T cells do is to literally recognize 00:27.610 --> 00:31.281 when one of our own cells is infected by something 00:31.281 --> 00:32.699 and destroy that cell. 00:33.867 --> 00:37.996 - Our cancer cells aren't always that much different from our normal cells. 00:38.163 --> 00:40.999 Our immune system is just not recognizing 00:40.999 --> 00:44.377 these cancer cells as foreign enough to attack them. 00:44.586 --> 00:46.796 - So we can take T cells out of the body, 00:46.796 --> 00:52.052 and we can engineer them to recognize the specific molecules on a particular cancer 00:52.677 --> 00:56.473 and once a T cell recognizes something, it can destroy it. 00:57.140 --> 01:02.604 - FDA approval for these cells are for diseases really of the blood system. 01:02.645 --> 01:04.773 So hematologic neoplasms. 01:04.773 --> 01:07.817 - Many of them are of B cells which are a different part of the immune system. 01:07.817 --> 01:11.279 But when those cells become cancerous, which can happen, 01:11.279 --> 01:13.573 these CAR Ts are very effective for those 01:13.615 --> 01:15.742 and many of these patients have actually been cured. 01:16.659 --> 01:19.162 - Because of the nature of the illnesses, 01:19.162 --> 01:21.206 or the similarities in illnesses 01:22.290 --> 01:25.502 CAR T are being investigated in autoimmune diseases 01:25.543 --> 01:28.546 for certain diseases like lupus, 01:28.671 --> 01:32.175 scleroderma, even multiple sclerosis, 01:32.175 --> 01:36.304 and we have active trials for all of those diseases at Yale. 01:40.558 --> 01:43.144 - T cells and B cells are part of the adaptive immune system. 01:43.144 --> 01:45.522 The B-cell produces novel antibodies 01:45.522 --> 01:48.316 each time it receives new signals from its T cell. 01:48.316 --> 01:52.904 Without the B cell, you'd be unable to adapt to new invaders, new viruses. 01:53.029 --> 01:56.741 But what happens with lupus is the immune system learns to cause 01:56.741 --> 02:00.995 inflammation to self proteins and tissues, and this in turn causes organ damage, 02:01.079 --> 02:04.791 loss of function, and in some cases can be a life threatening illness. 02:06.334 --> 02:10.630 We need to be in a position where we can have a precision diagnosis 02:10.630 --> 02:14.425 and accurate or precision therapies that are effective 02:14.467 --> 02:18.096 for the variety of organs that can be involved in lupus. 02:19.180 --> 02:22.058 - The idea with the autoimmune diseases 02:22.058 --> 02:26.187 is that the cells that we're targeting are actually quite similar 02:26.229 --> 02:31.025 to the cells that we are targeting with our CAR T for cancers. 02:32.026 --> 02:34.070 - When we use the word autoimmune, 02:34.070 --> 02:35.989 it's the immune system has learned 02:35.989 --> 02:38.992 to produce inflammation to self tissue. 02:39.617 --> 02:44.998 But once the immune cell is educated, for lack of a better word, against self, 02:44.998 --> 02:48.251 the inflammation is hard to turn off or can occur sporadically, 02:48.251 --> 02:50.545 and it's difficult to remove that memory, 02:50.545 --> 02:55.300 and the idea in CAR T is to try to remove the memory around that autoimmunity. 02:56.009 --> 02:59.762 - The CAR T cells are targeted against these cells, 02:59.762 --> 03:04.434 and they don't really care if the cells are normal or malignant. 03:04.767 --> 03:09.022 - So once those cells reach zero, the bone marrow produces new B cells. 03:09.272 --> 03:12.650 Those B cells tend, at least in the initial studies, 03:12.650 --> 03:15.653 tend to be what we call naive B cells. 03:15.653 --> 03:18.656 They seem to have lost a hallmark of autoimmunity. 03:19.616 --> 03:22.869 - One of the major appeals to CAR T cells, 03:23.244 --> 03:25.914 as opposed to some other forms of immunotherapy, 03:25.914 --> 03:28.750 be it in malignancy or autoimmune disease, 03:28.750 --> 03:31.669 is that they're quite powerful. 03:31.669 --> 03:34.047 In many cases, the effect is lasting. 03:34.047 --> 03:37.508 We don't usually give CAR T cells more than once. 03:38.593 --> 03:41.804 - I think this is going to be extremely impactful for patients 03:41.804 --> 03:44.098 where they're having life threatening disease, 03:44.098 --> 03:45.433 and where the 3 or 4 medicines 03:45.433 --> 03:48.019 that are currently approved for lupus aren't working for them. 03:48.937 --> 03:51.689 - And for most patients, once they have the CAR T cells, 03:51.689 --> 03:53.691 there's no other therapy that's prescribed. 03:53.691 --> 03:56.861 So there's good biological reasons to think that 03:56.945 --> 03:59.906 the CAR T cells could be curing some of these patients.