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These donut holes not for someone with CV issues. You can end up with empty pan and broken heart. VNDAful music don't get played often like earthquakes in CA.
It took 40 years for neural network to do skin deep facial recognition. from 2X2 to 300X300 just to solve 5 holes visualization. It will take multiple 3000X3000 to see anything in TME.
Who wants gold plated donut holes with IL2 topping for 15c?
Cases of cancers will double in next few years.
DNA-repair mechanism
Moving forward, our team plans to confirm the presence of global TCR in human cells, and if confirmed, to explore whether in the future repair might be safely boosted to counter diseases of aging
https://www.azolifesciences.com/news/20220401/Researchers-show-how-proteins-form-DNA-repair-mechanism-in-living-bacteria.aspx
Is inhibigen junk?
The gene that has recently been linked to ALS is found in what was long referred to be “junk DNA” in the genome. This DNA covers up over 97% of the genome, although it was once dismissed as “junk” since it does not encode proteins.
Even though noncoding DNA is still considered the biological dark matter, it is now known to function as a critical instruction manual. It controls when genes in the coding DNA—those that code for proteins—are switched on and off, among other things.
https://www.azolifesciences.com/news/20220404/Noncoding-DNA-mutations-prevent-the-brain-from-amyotrophic-lateral-sclerosis.aspx
6th pt? NSCLC?
including late-breaking data from the TiTAN™ clinical trial for the neoantigen-targeted peripheral T cell therapy product candidate GEN-011
For future ref:
CAR T-Cell Levels The median time to peak CAR T-cell levels was
7 days (range, 2 to 233) after the axi-cel infusion (Table S10 and Fig. S5). The median peak CAR T-cell level was 25.84 cells per cubic millimeter, with CAR T cells remaining detectable in 12 of 30 patients (40%) who could be evaluated by 24
months. The CAR T-cell peak and area under the curve within the first 28 days after treatment correlated with response
6 days!! to clean up decade old TME
These iPSC-NK cells demonstrate better anti-tumor activity (against AML) and higher levels of IFN? and TNFa compared to primary peripheral blood-derived NK cells isolated from healthy donors. Additionally, our iPSC-NK cells demonstrated prolonged “serial killing” of AML cells up to six days.
https://www.abstractsonline.com/pp8/#!/10517/presentation/14665
Since these new ACT therapies will bankrupt Medicare, they should do better than this:
the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standardcare group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%.
Hollywood has more bystanders than TME
Expensive CAR with 1 headlight
Gilead priced Tecartus at $373,000, the same price tag its other cell therapy Yescarta has for a different form of advanced lymphoma.
Yescarta® (axicabtagene ciloleucel) CAR T-cell therapy for adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
https://www.businesswire.com/news/home/20220401005519/en
Let see how many pts GEN11 needs to show it takes large bites .
Nibbling on cancer:
882 participants with R/M HNSCC needed to show efficacy in KEYNOTE-048
For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS < 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup.
https://ascopubs.org/doi/full/10.1200/JCO.21.02198
3's company was lucky to have freshly made donuts ready for consumption when they suffered HPD.
If you ask the patients whose suffered hyperprogression after getting anti-Pd1, immunotherapy is no lifesaver. Big pharmas tout survival advantage, not the early deaths. It is big business with a dark side.
One can try to push TILs to work harder. Aging is a bitch.
SKYSCRAPER-02, the first randomized study of investigational anti-TIGIT immunotherapy tiragolumab in extensive-stage small cell lung cancer (ES-SCLC), did not meet its co-primary endpoint of progression-free survival
https://www.businesswire.com/news/home/20220329005953/en
Large position compared to Large smart fund managers
MORGAN STANLEY 12/31/2021 13,636 -2,033 -12.975% $17
I do have a large position. I believe every old biological clock needs external processes to keep on ticking. Low cost Personal genomic profiling is the first step.
You sounded like a Wainbright analyst One should invest inside their comfort zone, postings here are biased.
Name 1 ACT that don't need no gene editing, no keytruda, no small molecule, no supporting beams
Imitating cancer to fight cancer!!
Gene editing is used to increase the persistence of allogeneic T cells by enabling them to evade host T cell or natural killer (NK) cell surveillance. A conventional method of preventing host T cell rejection is to knockout (KO) the ß-2 microglobulin (ß2M) to diminish the expression of MHC class I protein.
Imitating cancer?
Gene editing is used to increase the persistence of allogeneic T cells by enabling them to evade host T cell or natural killer (NK) cell surveillance. A conventional method of preventing host T cell rejection is to knockout (KO) the ß-2 microglobulin (ß2M) to diminish the expression of MHC class I protein.
ACT KOL Refinitiv/Verus downgrades GENOCEA BIOSCIENCES ORD SHS from HOLD to SELL.
TILs remind me of bio investors, 95% bystanders
2500 May 20 calls@$2.5 traded.
Exchaustion markers havn't worked for bsAbs. Why would them work for TIL selection? Lipstick on the same pigs
2/61 PRs + 2 uPRs
Analysis of the pharmacokinetics of GEN1046 in patients showed that systemic levels peaked shortly after each infusion. Consistent with preclinical markers, IFN?, IFN-responsiveness chemokines CXCL9–11, proliferating and total effector memory CD8+ T cells, and activated NK cells increased in peripheral blood. Low doses (≤200mg) of the drug had greater increases in immune modulation compared to higher doses (≥400mg), consistent with known bell curves for trimer-forming bsAbs, which cannot effectively cross-link in conditions of agent excess.
https://acir.org/weekly-digests/2022/march/a-bispecific-targeting-pd-l1-and-4-1bb-shows-potential-from-culture-to-clinic
You should go work for Wainbright. They really need a knowledge base on ACT
A few rads + CD40 + anti-PD1 + CDX301 will be the best for pts who can't take lymphodepletion. It will be interesting to compare cohort A with the combo:
Eight patients had partial or complete regression of the treated tumor (Fig. 5a,b). At distant (untreated) tumors, two patients progressed, six patients had stable disease or minor (<50%) regressions lasting 3–18 months
Editing TILs is like cosmetic surgery on same tied old men with lipstick
Neoantigens in Hematologic Malignancies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033457/
Atlas should be used to profile the pts who progressed after CART. 1 inhibigen costs 1 life.
axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40?patients with high-risk LBCL.
According to protocol, the primary efficacy analysis was performed after all treated patients were followed for ≥6?months after the first post-infusion disease assessment, and included patients with centrally confirmed disease type (double- or triple-hit lymphomas) or IPI score ≥3 who received a target dose of 2?×?106 CAR T?cells?kg–1. Among the 37?patients included in primary efficacy analysis, the primary endpoint of CRR was 78% (95% CI, 62–90; Fig. 1a). The median time to first complete response (CR) was 30?days (range, 27–207). The secondary endpoint of ORR was 89% (95% CI, 75–97) and the median time to first objective response was 29?days (range, 27–207). As of the data cutoff date, 25?patients (86% of complete responders and 68% of patients in primary efficacy analysis) had an ongoing CR while 27?patients (82% of objective responders and 73% of patients in the primary efficacy analysis) had an ongoing objective response.
Five patients experienced disease progression after an initial response to axi-cel at the time of data cutoff: one patient was retreated with axi-cel and achieved partial response (PR); two patients received subsequent therapies and did not respond; one patient was screened for axi-cel retreatment and is awaiting treatment; and one patient is still alive as of the data cutoff date, with subsequent therapies unknown.
Smart fund managers had no more GNCA to dump?
Lymphodepletion is critical. Removing Treg is just part of the unfolding story.
Results PT1, infused with predominantly CD4+ TIL (88%), achieved a complete response (CR) despite lack of IFN? detection with conventional in vitro tumor co-culture methods.
Inhibigen has 1,647 Followers, 0 Immunotherapy KOL
Thomas Davis
Well, we have been dosing patients now for some time. So there will be the durability in those patients over time, but it's really the initial response that's going to be most important. And remember that the key hurdles with these cell therapies stretches across the spectrum from safe infusion to proliferation of resistance of the cells in patients, which really can define the future. So there is a good amount of data that we'll be able to share that will give you a sense of the potential for GEN-011.
AE And discontinuation doubled to pay for longer pfs.
The trial met its primary endpoint, progression-free survival (PFS), and Opdualag more than doubled the median PFS when compared to nivolumab monotherapy, 10.1 months (95% Confidence Interval [CI]: 6.4 to 15.7) versus 4.6 months (95% CI: 3.4 to 5.6); (Hazard Ratio [HR] 0.75; 95% CI: 0.62 to 0.92, P=0.0055).1 The Opdualag safety profile was similar to that previously reported for nivolumab.1,2 No new safety events were identified with the combination when compared to nivolumab monotherapy.1,2 Grade 3/4 drug-related adverse events were 18.9% in the Opdualag arm compared to 9.7% in the nivolumab arm.2 Drug-related adverse events leading to discontinuation were 14.6% in the Opdualag arm compared to 6.7% in the nivolumab arm.2
https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx
Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy
https://www.nature.com/articles/s41591-022-01702-9?utm_source=twitter&utm_medium=social&utm_content=organic&utm_campaign=NRRJ_2_SJB_nrclinonc_editorial_socialposts
Treatment with anti-PD-L1 leads to clonal expansion of leukemia-specific CD4+ T-cells with the afore-mentioned helper/cytotoxic phenotype, as well as reduced expression of exhaustion markers.
https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2021015341/484383/Combining-nilotinib-and-PD-L1-blockade-reverses?redirectedFrom=fulltext
Using exchaustion markers to select TILs for expansion is as good as the bi-specific Abs.
In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8+ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8+ lymphocytes