Possible ways forward for Car T 5T4 combinations ?
Dr. Eileen Parkes of Queen's University in Belfast
We and others had previously shown that you need STING to upregulate expression of PD-L1, the ligand for PD-1. And cancers with high PD-L1 expression, we already knew, are those that are most likely to respond to immune checkpoint blockade. Moreover, given STING's role in turning on the immune system, it's a very neat way of making a cold tumor hot
Novartis embarked on this first-in-human trial as an important first step in characterizing the safety profile and mechanism of ADU-S100 and its ability to activate the STING pathway. HTTps://www.creative-biolabs.com/blog/car-t/car-t-armored-with-pd-1-antibody/ HTTps://jamanetwork.com/journals/jama/fullarticle/2714651?utm_source=twitter&utm_medium=social_jama&utm_term=1882413654&utm_content=followers-article_engagement-illustration_medical&utm_campaign=article_alert&linkId=59319702 HTTps://www.bloomberg.com/news/articles/2018-03-01/merck-turns-to-tumor-killing-viruses-in-immune-cancer-treatment HTTps://endpts.com/turning-cold-tumors-hot-checkmate-pharma-outlines-its-initial-success-story-at-aacr18/
A personalized cancer treatment vaccine that targets patient-specific tumor neoantigens showed it could stimulate a potent anti-tumor response in melanoma patients who were at high risk for recurrence following surgery.
Dana-Farber researchers led by Catherine J. Wu, MD, and Patrick A. Ott, MD, PhD, reported in 2017 on six patients who received the vaccine, called NeoVax. The vaccine was created using neoantigen peptides from the patients’ melanoma tumors. When injected into the patients, the vaccine spurred responses by immune T cells, both helper and killer T cells, that recognized the neoantigens on the tumor cells. Four of the six patients had no recurrence of the cancer at a median of 25 months. Two patients had recurrences, but were then treated with the checkpoint inhibitor pembrolizumab, resulting in complete disappearance of their cancer. The researchers say these outcomes support the idea of a doublepunch against tumors: using vaccines to rev up an immune response combined with checkpoint blockers to release the brakes. HTTp://blog.dana-farber.org/insight/2018/06/enhancing-immunotherapy-race-make-cold-tumors-hot/
the team used biodegradable liposome-based nanoparticles to carry immune-boosting drugs directly to solid tumors and open a window for CAR T cells to be more effective in preclinical models of breast and brain cancer.
The nanoparticles “are not supposed to replace conventional CAR T-cell therapy,” said Dr. Matthias Stephan, who led the study. Instead, he envisions that “you could use these nanoparticles to precondition the patient, and precondition the tumor, so that your T cells work much better. HTTps://www.fredhutch.org/en/news/center-news/2018/07/liposome-nanoparticles-tumors-vulnerable-immunotherapy.html