CAR-T Cell Therapy for Lupus

Transcript

• 00:03- CAR-T cells are a relatively new treatment
• 00:06that's FDA approved for cancers.
• 00:09So this is a treatment where normal immune cells are modified
• 00:13so that they can identify and kill cancer cells.
• 00:18- Amongst the many, many types of cells that are part of the immune system,
• 00:22one type are called T cells.
• 00:23One of the things that T cells do is to literally recognize
• 00:28when one of our own cells is infected by something
• 00:31and destroy that cell.
• 00:34- Our cancer cells aren't always that much different from our normal cells.
• 00:38Our immune system is just not recognizing
• 00:41these cancer cells as foreign enough to attack them.
• 00:45- So we can take T cells out of the body,
• 00:47and we can engineer them to recognize the specific molecules on a particular cancer
• 00:53and once a T cell recognizes something, it can destroy it.
• 00:57- FDA approval for these cells are for diseases really of the blood system.
• 01:03So hematologic neoplasms.
• 01:05- Many of them are of B cells which are a different part of the immune system.
• 01:08But when those cells become cancerous, which can happen,
• 01:11these CAR Ts are very effective for those
• 01:14and many of these patients have actually been cured.
• 01:17- Because of the nature of the illnesses,
• 01:19or the similarities in illnesses
• 01:22CAR T are being investigated in autoimmune diseases
• 01:26for certain diseases like lupus,
• 01:29scleroderma, even multiple sclerosis,
• 01:32and we have active trials for all of those diseases at Yale.
• 01:41- T cells and B cells are part of the adaptive immune system.
• 01:43The B-cell produces novel antibodies
• 01:46each time it receives new signals from its T cell.
• 01:48Without the B cell, you'd be unable to adapt to new invaders, new viruses.
• 01:53But what happens with lupus is the immune system learns to cause
• 01:57inflammation to self proteins and tissues, and this in turn causes organ damage,
• 02:01loss of function, and in some cases can be a life threatening illness.
• 02:06We need to be in a position where we can have a precision diagnosis
• 02:11and accurate or precision therapies that are effective
• 02:14for the variety of organs that can be involved in lupus.
• 02:19- The idea with the autoimmune diseases
• 02:22is that the cells that we're targeting are actually quite similar
• 02:26to the cells that we are targeting with our CAR T for cancers.
• 02:32- When we use the word autoimmune,
• 02:34it's the immune system has learned
• 02:36to produce inflammation to self tissue.
• 02:40But once the immune cell is educated, for lack of a better word, against self,
• 02:45the inflammation is hard to turn off or can occur sporadically,
• 02:48and it's difficult to remove that memory,
• 02:51and the idea in CAR T is to try to remove the memory around that autoimmunity.
• 02:56- The CAR T cells are targeted against these cells,
• 03:00and they don't really care if the cells are normal or malignant.
• 03:05- So once those cells reach zero, the bone marrow produces new B cells.
• 03:09Those B cells tend, at least in the initial studies,
• 03:13tend to be what we call naive B cells.
• 03:16They seem to have lost a hallmark of autoimmunity.
• 03:20- One of the major appeals to CAR T cells,
• 03:23as opposed to some other forms of immunotherapy,
• 03:26be it in malignancy or autoimmune disease,
• 03:29is that they're quite powerful.
• 03:32In many cases, the effect is lasting.
• 03:34We don't usually give CAR T cells more than once.
• 03:39- I think this is going to be extremely impactful for patients
• 03:42where they're having life threatening disease,
• 03:44and where the 3 or 4 medicines
• 03:45that are currently approved for lupus aren't working for them.
• 03:49- And for most patients, once they have the CAR T cells,
• 03:52there's no other therapy that's prescribed.
• 03:54So there's good biological reasons to think that
• 03:57the CAR T cells could be curing some of these patients.