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Nanomedicine Folks - Fascinating study by Dr. Ivkov's lab at @HopkinsMedicine @JohnsHopkins addressing: How does nanoparticle targeting work to cause tumour reduction? Nothing to do with cancer cell targeting. Everything to do with immune status [1/n] https://advances.sciencemag.org/content/6/13/eaay1601
[2/n] 1) NPs with antibodies dont reach cancer cells any more effectively. But antibody-NPs accumulate more in tumours than bare NPs. Fantastic use of multiple mouse models with varying levels of Her2 expression showed very interesting results. NPs colocalize with immune cells.
![[2/n] 1) NPs with antibodies dont reach cancer cells any more effectively. But antibody-NPs accumulate more in tumours than bare NPs. Fantastic use of multiple mouse models with varying levels of Her2 expression showed very interesting results. NPs colocalize with immune cells.](https://pbs.twimg.com/media/EU3UpJBXYAEwK5O.jpg "[2/n] 1) NPs with antibodies dont reach cancer cells any more effectively. But antibody-NPs accumulate more in tumours than bare NPs. Fantastic use of multiple mouse models with varying levels of Her2 expression showed very interesting results. NPs colocalize with immune cells.")
[3/n] The immune status of the mouse background matters. Competent immune status mice accumulate more in tumours compared to tumours in nude and NSG mice. Inside tumours,Pro-Inflam TAMs, Neutrophils, NK cells, T cells take up most of the NPs in the first 24 hours.
![[3/n] The immune status of the mouse background matters. Competent immune status mice accumulate more in tumours compared to tumours in nude and NSG mice. Inside tumours,Pro-Inflam TAMs, Neutrophils, NK cells, T cells take up most of the NPs in the first 24 hours.](https://pbs.twimg.com/media/EU3VwS3X0AAvDHE.png "[3/n] The immune status of the mouse background matters. Competent immune status mice accumulate more in tumours compared to tumours in nude and NSG mice. Inside tumours,Pro-Inflam TAMs, Neutrophils, NK cells, T cells take up most of the NPs in the first 24 hours.")
[4/n] Over the course of days, the immune microenvironment changes and CD8 T cells seem to be recruited and proposed to be causing the tumour growth reduction. Reduction seen in intact immune models and not in athymic. Even the untargeted NP showed some reduction! Mind blowing.
![[4/n] Over the course of days, the immune microenvironment changes and CD8 T cells seem to be recruited and proposed to be causing the tumour growth reduction. Reduction seen in intact immune models and not in athymic. Even the untargeted NP showed some reduction! Mind blowing.](https://pbs.twimg.com/media/EU3Wjt1X0AADiq8.jpg "[4/n] Over the course of days, the immune microenvironment changes and CD8 T cells seem to be recruited and proposed to be causing the tumour growth reduction. Reduction seen in intact immune models and not in athymic. Even the untargeted NP showed some reduction! Mind blowing.")
[5/n] If you deplete the immune cells using a pan-leuk inhibitor, tumour accumulation goes down. The changes in immune cells are very interesting and point towards some sort of underlying cross-talk to cause this CD8 infiltration.
![[5/n] If you deplete the immune cells using a pan-leuk inhibitor, tumour accumulation goes down. The changes in immune cells are very interesting and point towards some sort of underlying cross-talk to cause this CD8 infiltration.](https://pbs.twimg.com/media/EU3YATKWoAcJMSW.jpg "[5/n] If you deplete the immune cells using a pan-leuk inhibitor, tumour accumulation goes down. The changes in immune cells are very interesting and point towards some sort of underlying cross-talk to cause this CD8 infiltration.")
[6/n] Many great questions for followup: a) What about PEGylated NPs? Is the affect in paper because of dextran coating? b) Tumour cytokine profile? c) What is the role of Tregs? d) What if you use Ab without Fc? e) Does imaging support CD8 mediated cancer death? f) Dose effect?
[7/n] This is a role model study for Cancer nano. This is the kind of stuff we need in the field exactly! The group went to great efforts in selecting tumour models, NP-IgG controls, generating HuHer model, time profile of cells, large n etc. MUST READ for Cancer Nano people.
