Howard Smith MD, AMMar 11, 2025
Improving Ovarian Cancer Immunotherapy: Cancer immunologists at the University of Virginia have now discovered what underlies this failure. #immunotherapy #checkpointinhibitor #ovarian #cancer #biome #flagellin
https://www.instagram.com/reel/DHDygk-shuL/
Howard G. Smith MD, AM on Instagram: "Improving Ovarian Cancer Immunotherapy Immunotherapy has been a resounding success for melanoma skin cancer and small cell lung cancer. Not so for ovarian cancer. Cancer immunologists at the University of Virginia have now discovered what underlies this failure. Their research discovered that flagellin protein from gut bacteria blocks the effectiveness of the checkpoint inhibitors that power most current immunotherapy. This bacterial flagellin inhibits immune cell communication helping tumors flourish rather than die. Using a mouse model and blocking flagellin action restored immunotherapeutic effectiveness with 80% of treated animals enjoying long-term tumor control. If this approach is effective for human ovarian cancer patients, coupling flagellin blocking with checkpoint immunotherapy may be a winning therapeutic strategy …..someday soon. https://newsroom.uvahealth.com/2025/02/11/ovarian-cancer-discovery-could-turn-ailed-treatment-into-lifesaver/ https://aacrjournals.org/cancerimmunolres/article-abstract/doi/10.1158/2326-6066.CIR-24-0513/751676/TLR5-signaling-causes-dendritic-cell-dysfunction?redirectedFrom=fulltext #immunotherapy #checkpointinhibitor #ovarian #cancer #biome #flagellin"

0 likes, 0 comments - drhowardsmithreports on March 11, 2025: "Improving Ovarian Cancer Immunotherapy Immunotherapy has been a resounding success for melanoma skin cancer and small cell lung cancer. Not so for ovarian cancer. Cancer immunologists at the University of Virginia have now discovered what underlies this failure. Their research discovered that flagellin protein from gut bacteria blocks the effectiveness of the checkpoint inhibitors that power most current immunotherapy. This bacterial flagellin inhibits immune cell communication helping tumors flourish rather than die. Using a mouse model and blocking flagellin action restored immunotherapeutic effectiveness with 80% of treated animals enjoying long-term tumor control. If this approach is effective for human ovarian cancer patients, coupling flagellin blocking with checkpoint immunotherapy may be a winning therapeutic strategy …..someday soon. https://newsroom.uvahealth.com/2025/02/11/ovarian-cancer-discovery-could-turn-ailed-treatment-into-lifesaver/ https://aacrjournals.org/cancerimmunolres/article-abstract/doi/10.1158/2326-6066.CIR-24-0513/751676/TLR5-signaling-causes-dendritic-cell-dysfunction?redirectedFrom=fulltext #immunotherapy #checkpointinhibitor #ovarian #cancer #biome #flagellin".

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Thiago CarvalhoJun 22, 2024

This one is for adults with primary advanced or recurrent endometrial cancer.

"This new approval is based on data from the Phase 3 NRG-GY018 trial, also known as KEYNOTE-868. Results reported last year in the New England Journal of Medicineshowed a 70% lower risk of disease progression when patients were treated with pembrolizumab and chemotherapy."
#Immunology #Immunotherapy #CheckpointInhibitor
https://www.cancerresearch.org/blog/june-2024/keytruda-receives-40th-fda-approval?utm_source=Social&utm_medium=LinkedIn&utm_campaign=CRI&utm_id=CRI

Keytruda Receives 40th FDA Approval - Cancer Research Institute

This week marked a significant milestone in the fight against cancer. On June 17, the FDA approved the cancer immunotherapy drug, pembrolizumab (Keytruda®), combined with chemotherapy, for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This marks the 40th approval for Merck‘s drug, which has already been approved for treating various […]

Cancer Research Institute
Thiago CarvalhoFeb 1, 2024

"Novartis’ anti-TIM-3 antibody has flunked a phase 3 blood cancer trial, prompting the Swiss drugmaker to pull the drug candidate from its pipeline. The failed study was the biggest test to date of an immuno-oncology target into which a who’s who of leading drug developers have pumped money."
#Immunology #immunotherapy #CheckpointInhibitor

https://www.fiercebiotech.com/biotech/novartis-calls-time-tim-3-axing-cancer-candidate-after-phase-3-flop

Novartis calls time on TIM-3, axing cancer candidate after phase 3 flop

Novartis’ anti-TIM-3 antibody has flunked a phase 3 blood cancer trial, prompting the Swiss drugmaker to pull the drug candidate from its pipeline. | Novartis’ anti-TIM-3 antibody has flunked a phase 3 blood cancer trial, prompting the Swiss drugmaker to pull the drug candidate from its pipeline. The failed study was the biggest test to date of an immuno-oncology target into which a who’s who of leading drug developers have pumped money.

Fierce Biotech
Thiago CarvalhoDec 3, 2023

AlphaFold & PDL1

"Here, we test a protein design pipeline that uses iterative rounds of deep learning (DL)-based structure prediction (AlphaFold2) and sequence optimization (ProteinMPNN) to design autoinhibitory domains (AiDs) for a PD-L1 antagonist."
#Immunology #CheckpointInhibitor

https://www.pnas.org/doi/10.1073/pnas.2307371120

Thiago CarvalhoOct 20, 2023

The effects of the CTLA4 deletion were not very surprising, what's fascinating here is how it compares to the double mutants (PD1/CTLA4).

"CTLA4 disrupted CART19 cells display prolonged surface CAR expression, increased proliferation, and enhanced CART19 effector function supported by unopposed CD28 co-stimulation, which is lost in CART19 cells deficient for both PD-1 and CTLA4"

#Immunology #Immunotherapy #CheckpointInhibitor #CTLA4 #CARTcells

https://www.cell.com/immunity/fulltext/S1074-7613(23)00407-7#secsectitle0075

Alan KotokAug 3, 2023

A clinical trial assessing a synthetic antibody to generate an immediate response and also generate a more durable treatment for solid tumor cancers, advanced to a mid-stage study.

https://sciencebusiness.technewslit.com/?p=45068

#News #Press #Science #Business #Cancer #Biotechnology #ClinicalTrial #Immunotherapy #AdverseEffects #CheckpointInhibitor #Antibody #ImmuneSystem #TCells #InnateImmuneSystem

Trial Advances of Dual-Action Cancer Immunotherapy

A clinical trial assessing a synthetic antibody to generate an immediate response and also generate a more durable treatment for solid tumor cancers, advanced to a mid-stage study.

Science and Enterprise
Mathieu DesgroseilliersMay 3, 2023

Very interesting case report of pulse methylprednisolone in treatment of steroid-refractory #Immune #CheckPointInhibitor #pneumonitis

We also treated a patient with a grade IV pneumonitis with high dose steroid. My observation is a very rapid improvement, within 48h.

Further research is needed but it could be promising for life-threatening immune checkpoint inhibitor reaction

https://pubmed.ncbi.nlm.nih.gov/36119082/

#MedMastodon #FOAMcc #FOAMed

Pulse corticosteroid therapy in the treatment of steroid-refractory immune checkpoint inhibitor-related pneumonitis: Case report and review - PubMed

Immune checkpoint inhibitors (ICIs) have demonstrated promising therapeutic outcomes in treating a variety of malignancies, but immune-related adverse events (irAE) may develop. Among all the irAE, immune-related pneumonitis was relatively common and life-threatening. High-dose corticosteroid was re …

PubMed
Christian TidonaDec 19, 2022

What if we could trace #cytotoxic #Tcells throughout the human body before and during #cancer #immunotherapy?

Researchers at the University of Groningen have used a CD8-specific positron emission tomography (#PET) tracer in a phase 1/2 clinical trial. Patients with solid tumors were imaged before and ~30 days after starting treatment with #antibodies against PD-L1, PD-1, and/or CTLA-4.

Article in Nature Medicine: https://www.nature.com/articles/s41591-022-02084-8

#checkpointinhibitor #solidtumor #clinicaltrial

Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial - Nature Medicine

A CD8-specific, one-armed antibody positron emission tomography tracer enables the visualization of the immune response in patients with solid tumors before and after starting immunotherapy.

Nature
Thiago CarvalhoNov 9, 2022

"Won et al. demonstrate that PD1
inhibitor treatment alone induces
myocarditis in A/J mice, creating a mouse model for immune-checkpoint-inhibitor-associated myocarditis."

#Immunology #Immunotherapy #CheckpointInhibitor

https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01480-2?rss=yes&utm_source=dlvr.it&utm_medium=twitter