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I’m way too sick to try to reword this (below quotes from Gavin Giovannoni, a neurologist who writes about MS) but it’s adding to a lot of what’s been discussed with ME and I just want to put it out there. He’s talking about CAR-T cells and AHSCT as immune reconstitution therapies that may work better than other MS treatments like rituximab, and why they might work better (Car-t cells more than AHSCT).
I’m really hoping they study car-t cells in MS soon. And if it works well then hopefully ME. If anyone with lupus and ME has tried it I hope they post!
“What was not mentioned or acknowledged is the fact that anti-CD20 therapies don’t penetrate the CNS to any significant degree (please see ‘Anti-CD20 Kool-Aid’, 11-Sept-2021). In contrast, CAR T-cells will get into the CNS and potentially scrub it clean of B-cells. This is one of the major distinctions between CAR T-cells and anti-CD20 therapies. There is also a large body of evidence in the scientific literature on CNS B-cells and the antibodies they produce as being pathogenic and one of the drivers of smouldering MS. So it makes sense to go beyond peripheral B-cell depletion to target CNS B-cells and their antibody products.
The other big issue that was ignored was the potential causal role of EBV plays in driving MS disease activity (please see ‘More evidence that EBV causes MS’, 6-Sept-2022). If EBV is the driver, CD19-targeted CAR T-cells will purge the body of EBV-infected B-cells, including the CNS and other deep tissue compartments such as the deep cervical lymph nodes. If a specific strain of EBV is causing MS, CD19-targeted CAR T-cells could cure MS by depleting latently EBV-infected B-cells and eliminating the virus from the body. This is why I am so excited about CAR T-cell technology and have spent the best part of 2 years trying to get the pharmaceutical industry to take their CAR T-cell technology into MS. The good news is that a few pharmaceutical companies are progressing with CAR T-cell studies in MS.”
“When you study the T-cell repertoire in pwMS, you find it quite restricted. In other words, pwMS have a reduced variety of T-cells in their peripheral blood. This means a fewer number of unique T-cell receptors to respond to foreign proteins or antigens. This reduced or truncated T-cell receptor repertoire is seen with age and is a marker of immunosenescence (ageing immune system). However, when pwMS undergo AHSCT, they widen or rejuvenate their T-cell repertoire. A recent study has shown that this widening T-cell repertoire also occurs in relation to EBV immunity. We hypothesised that AHSCT would do this a few years ago and planned to study this phenomenon in our STAR-MS trial.
What does this mean? I hypothesise that AHSCT is depleting the exhausted anti-EBV T-cells, and when immunosuppressed during the depletion phase of AHSCT, EBV reactivates from its latent to its lytic state, and the result is the production of infective virus. The reconstituting immune system then sees the infective EBV virus and stimulates new T-cell responses to control EBV. Importantly, these new T-cell responses are not exhausted and are very effective at killing and keeping EBV under control. These EBV-reactive T-cells are detected as being different from those present before AHSCT; this is what is meant by ‘diversification and widening’ of the EBV-reactive cytotoxic T-cell repertoire. If this hypothesis is correct, AHSCT acts as an EBV immunotherapy”
For background there’s this post on the lupus research https://forums.phoenixrising.me/thr...o-remission-in-severe-lupus-dec-9-2022.89191/
I’m really hoping they study car-t cells in MS soon. And if it works well then hopefully ME. If anyone with lupus and ME has tried it I hope they post!
“What was not mentioned or acknowledged is the fact that anti-CD20 therapies don’t penetrate the CNS to any significant degree (please see ‘Anti-CD20 Kool-Aid’, 11-Sept-2021). In contrast, CAR T-cells will get into the CNS and potentially scrub it clean of B-cells. This is one of the major distinctions between CAR T-cells and anti-CD20 therapies. There is also a large body of evidence in the scientific literature on CNS B-cells and the antibodies they produce as being pathogenic and one of the drivers of smouldering MS. So it makes sense to go beyond peripheral B-cell depletion to target CNS B-cells and their antibody products.
The other big issue that was ignored was the potential causal role of EBV plays in driving MS disease activity (please see ‘More evidence that EBV causes MS’, 6-Sept-2022). If EBV is the driver, CD19-targeted CAR T-cells will purge the body of EBV-infected B-cells, including the CNS and other deep tissue compartments such as the deep cervical lymph nodes. If a specific strain of EBV is causing MS, CD19-targeted CAR T-cells could cure MS by depleting latently EBV-infected B-cells and eliminating the virus from the body. This is why I am so excited about CAR T-cell technology and have spent the best part of 2 years trying to get the pharmaceutical industry to take their CAR T-cell technology into MS. The good news is that a few pharmaceutical companies are progressing with CAR T-cell studies in MS.”
“When you study the T-cell repertoire in pwMS, you find it quite restricted. In other words, pwMS have a reduced variety of T-cells in their peripheral blood. This means a fewer number of unique T-cell receptors to respond to foreign proteins or antigens. This reduced or truncated T-cell receptor repertoire is seen with age and is a marker of immunosenescence (ageing immune system). However, when pwMS undergo AHSCT, they widen or rejuvenate their T-cell repertoire. A recent study has shown that this widening T-cell repertoire also occurs in relation to EBV immunity. We hypothesised that AHSCT would do this a few years ago and planned to study this phenomenon in our STAR-MS trial.
What does this mean? I hypothesise that AHSCT is depleting the exhausted anti-EBV T-cells, and when immunosuppressed during the depletion phase of AHSCT, EBV reactivates from its latent to its lytic state, and the result is the production of infective virus. The reconstituting immune system then sees the infective EBV virus and stimulates new T-cell responses to control EBV. Importantly, these new T-cell responses are not exhausted and are very effective at killing and keeping EBV under control. These EBV-reactive T-cells are detected as being different from those present before AHSCT; this is what is meant by ‘diversification and widening’ of the EBV-reactive cytotoxic T-cell repertoire. If this hypothesis is correct, AHSCT acts as an EBV immunotherapy”
For background there’s this post on the lupus research https://forums.phoenixrising.me/thr...o-remission-in-severe-lupus-dec-9-2022.89191/
