Replies to post #20465 on Humanigen Inc (fka HGENQ)

[Knuckle Sandwich]

Here is what I have been looking at in relation to Car-T. I am not an expert and only learning as we go but this is a great summary of Lenzilumab in CD-19. This is very eye opening to the potential here in Car-T and where Lenzilumab is useful.


Author Saad S. Kenderian is with Mayo Clinic and holds patents in Car-T with Humanigen, and Novartis I believe.

Conflict-of-interest disclosure: S.S.K. is an inventor on patents in the field of CAR-T cell therapy that are licensed to Novartis (under an agreement among the Mayo Clinic, the University of Pennsylvania, and Novartis). O.A., T.S., D.C., and C.D. are employed by Humanigen. R.M.S., R.S., M.J.C., and S.S.K. are inventors on patents related to this work. The remaining authors declare no competing financial interests.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376281/

[archefal]

I don't think so, unfortunately. Part of CAR T administration is preconditioning w chemotherapy to lymphodeplete - i.e., kill the patient's "regular" immune cells so when the CAR T cells are reinfused, they have an evolutionary niche to expand into. Basically, they have more resources and less competition from their normal cells that are less effective at fighting the cancer. This sounds like the pt had some latent viral infections that reactivated upon lymphodepletion, probably taking advtg of the opportunity presented by attenuated immune surveillance. I don't know if lenz would help in this circumstance since it wasn't exactly CRS that killed them (resolved in 5 days)

Just my opinion, though. Happy to be proven wrong

[archefal]

also relevant - potentially moreso - pt. had neutropenia which is life-threatening. I would postulate additional myelosuppression w/ lenz would actually make this worse

[cowtown jay]

"Is this a situation where an antibody like Lenz could have helped the outcome?"

I don't have a science background, but I have observations from my wife's case, which include a background of cancer, radiation, chemo, and surgery.

The day after the PET/CT scans, which showed a complete response, yet the patient required hospitalization immediately thereafter, he was already presenting with signs of some type of encephalopathy, which was the short-term memory loss, confusion, and obtundation, leading to intubation. I don't know if this happened as a toxic side effect of CTX-110, or not. If so, we ought to be looking at Crispr in terms of being used as a co-therapy with their product, as we are with Kite/Gilead.

But those are symptoms which I think could have been alleviated with lenz.

The problem in this case, for the doctors and oncologists to study, is the febrile neutropenia. Lenz works on shutting down the over-production of white blood cells. This patient suffered by a low white blood cell count.

Would it have been effective once the patient was found to have reactivated HHV-6 encephalitis, in combination with the anti-viral therapy that was then administered?

In a broader sense, my question is how do we ensure that lenz doesn't deprive patients of the white blood cells they need, in our quest to prevent the over-production of those white blood cells?