Immunity
| Line of Defense | Timeline | Cells | Antigen Dependency | Examples | |
|---|---|---|---|---|---|
| Innate (non-specific) | First | Immediate response (0 -96 hours) | Natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils | Independent | Skin, hair, cough, mucous membranes, phagocytes, granulocytes |
| Adaptive (specific) | Second | Long term (>96 hours) | T and B lymphocytes | Dependent | Pus, swelling, redness, pain, T and B lymphocyte response |
Autoimmunity (Autoantibody)
Evidence
| Human | CSF derived auto-Abs that react with DA in SN were present in 78% vs. 3% of PD patients and controls, respectively [12]. | ||
| (Benkler, 2012 #780) | 77 sPD | Serum:
| |
| Microglial activation through an FCγ-receptor pathway can be induced by IgG derived from PD patients, which subsequently causes substantia nigra cell injury [16]. | |||
| animal | Chen et al. [15] who elegantly exemplified autoimmunity utilizing IgG antibodies derived from PD patients to induce Parkinson-like pathology in an experimental animal model |
ImmunoPET
| {Sehlin, 2019 #799, Review} | intracellular 는 challenge라는데) eg aSyn | One potential challenge is that the majority of aggregated a-syn in the brain appears to be intracellular; and thus an additional barrier has to be conquered by the bispecific antibody in order to reach its primary target |
| {Wei, 2020 #1801} review | Focus only on tumor | |
| Saiz-López 2021 | CPP-Nanobody Feasibility study | |
| p 1 | Feasibility of transferrin usae | The feasibility for the 1st step can be completed by end of 2021/beginning of 2022 |
| p 2 | Conjugation of biologic (parkin An) → look at biodistribution | Check antibody list (Takeshi) |
| p 3 | Animal model (looking at ?htag? radio-labeling?) |
Nanobody + chelator radiolabel schematic showing chelator with isotopes 89Zr, 64Cu, 68Ga, 52Mn, 86Y, 66Ga, 44Sc, [18F]AlF.
Imnewrun
| BBB penetration platform | Transferrin receptor
|
| Anti-PD-L1 Antibody | Tau 조절은 실험중 |
| D in vivo live imaging (chronic? 90m?) | Patented |
| meeting before JPM 2021 | |
| early research collaboration |
both hope early research collaboration with Takeda.
[Imnewrun]
They have BBB penetration platform. Like Denali, they utilize endothelial transferrin receptors for receptor mediated endocytosis. I think we may want to compare this to Denali’s modality. Using this platform technology, they are developing Anti-PD-L1 antibody targeting Alzheimer’s disease. They saw AB reduction in mice and are now looking at the effect on tau. They are wondering that, if Takeda is interested in any form of research collaboration opportunity with them, they would like to explore an opportunity to have a conversation with Takeda before JPM 2021 Jan.
In vitro drug sensitivity testing (DST)
The potential efficacy of individualised chemotherapy is tested by in vitro drug sensitivity testing (DST) in each patients before entering the trial.
https://www.ncbi.nlm.nih.gov/books/NBK67946/
Inflammation
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
ImmunoPET / Saiz-López 2021 | the row label reads Saiz-López 2021; preserved verbatim. | low confidence on Saiz vs Sáiz accent. |
Imnewrun / BBB penetration platform / Angiochem ( a Canadian company's Angiopep2-FITC) | reads Angiochem ( a Canadian company's Angiopep2-FITC); preserved verbatim. | low confidence on company name spelling. |