Chat GPT answer as to possible reasons for the dev

Chat GPT answer as to possible reasons for the development of these anti-drug anti-bodies

Quote:

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"When using adeno-associated virus (AAV) technology to deliver a gene that allows the body to produce a therapeutic protein like leronlimab, the immune system can sometimes recognize the newly produced protein as foreign, leading to the production of antibodies against it. Here’s why this might happen:

Immune System Recognition: Even though leronlimab is a therapeutic antibody designed to target specific human proteins, it's still possible for the immune system to recognize it as foreign, especially if it's being produced in a way that is atypical for the body. This recognition could lead to the development of anti-drug antibodies (ADAs).

Protein Structure Differences: The AAV vector might cause slight variations in how leronlimab is produced compared to how it would be if manufactured outside the body. These structural differences, even if minor, could make the protein appear foreign to the immune system.

Pre-existing Immunity: If a person has previously been exposed to leronlimab (e.g., through previous treatments), their immune system might have developed memory B cells that quickly produce antibodies against leronlimab upon re-exposure.

Autoimmunity or Breakdown of Tolerance: In rare cases, the body's tolerance mechanisms might fail, leading the immune system to target proteins that are actually self-made, which could include therapeutically produced proteins like leronlimab.

Vector Immunogenicity: The AAV vector itself can sometimes trigger an immune response, and this can lead to a broader immune activation that might include the production of antibodies against the delivered therapeutic protein.

In summary, the production of anti-leronlimab antibodies after using AAV technology could result from the immune system's recognition of the newly produced protein as foreign, potential structural differences in the protein, or broader immune responses triggered by the gene therapy vector."

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So, in consideration of this, I suspect that if you dose LL weekly, those anti-drug antibodies would attack the leronlimab that was subcutaneously injected as well as the leronlimab that was produced inside the body. This of course would weaken RO and I don't know if you could still guarantee 100% RO in such a situation.

In order for the immune system to develop antibodies at all, something had to tell the system that the leronlimab it was seeing was foreign. The leronlimab manufactured outside the body is not typically perceived as foreign and anti-drug antibodies are not typically a problem when subcutaneously injected.

i'd suspect that it has more to do with the difference in the produced leronlimab within the body vs. the injected leronlimab that is causing the development of these antibodies.

Auto-immune disease really is a ramped up immune system against yourself. For some reason, your immune system thinks some part of your body is foreign and then develops a response against it. Well maybe these individuals have an Active Immune System and possibly, what you're suggesting, giving LL along side to bring it down to normal, might prevent that development of anti-drug antibodies.

Maybe we will find the answer in the coming Inflammation / Immune Activation Trial