tag:blogger.com,1999:blog-6821948329541212415.post2714377919423461167..comments2024-02-24T03:48:31.640-05:00Comments on NIHilist's Immunology: Immunotoxins show anti-cancer synergy with immune checkpoint inhibitorsDavid Usharaulihttp://www.blogger.com/profile/02668672470276307921noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-6821948329541212415.post-23046453821773300902015-12-02T20:50:53.222-05:002015-12-02T20:50:53.222-05:00It is my understanding [based on this study] that ...It is my understanding [based on this study] that this particular toxin-conjugated HER2 antibody induces so called "immunogenic" cell death and allows priming against mutant antigens released from dying cancer cells [ and once it is taken up by professional antigen presenting cells]. CTLA4/PD1 will then simply amplify this anti-cancer response.David Usharaulihttps://www.blogger.com/profile/02668672470276307921noreply@blogger.comtag:blogger.com,1999:blog-6821948329541212415.post-63430214211785064972015-12-02T20:39:14.404-05:002015-12-02T20:39:14.404-05:00I was surprised at the immunological response to T...I was surprised at the immunological response to T-DM1. The other two mAbs (presumably Nivolumab and Ipilimumab) are well known in theory and practice to elicit an enhanced immune response, but Trastuzumab itself isn't primarily known as an immune acting agent although its effect on the immune system has been studied. It would be interested to see why T-DM1 in particular combined so well and compare this to TKIs, naked Abs, taxane chemotherapies, and other ADCs; maybe it's because of the immune response native to Trastuzumab and the specificity of released antigens to just tumor cells (instead of a mix of normal cells and tumor cells as with taxanes) once some tumors have been killed.Unknownhttps://www.blogger.com/profile/18054891182346054370noreply@blogger.comtag:blogger.com,1999:blog-6821948329541212415.post-2882006296592460192015-12-02T20:24:14.358-05:002015-12-02T20:24:14.358-05:00Thanks for expressing your opinion.
For me this ...Thanks for expressing your opinion. <br /><br />For me this study has 2 major significance [the reasons I reviewed it]:<br /><br />1. triple Ab application primed "memory" response, suggesting that one [or two] time application should provide life-long immunity to the tumor. <br /><br />2. Presence of Foxp3 Tregs within tumor tissue or other tissues were necessary to prevent excessive inflammation when triple Ab were applied. David Usharaulihttps://www.blogger.com/profile/02668672470276307921noreply@blogger.comtag:blogger.com,1999:blog-6821948329541212415.post-25170285119372368882015-12-02T20:11:06.855-05:002015-12-02T20:11:06.855-05:00This is an interesting result, I wonder how it com...This is an interesting result, I wonder how it compares to other tumorcidal agents like TKIs or traditional taxane based chemotherapy. Perhaps the former don't have any native immune effect like a mAb does and the latter is not specific enough to prime DC's to just tumor cells. Page 31 of the presentation "ImmunoGen_10-27-15_for_website.pdf" has another demonstration of the synergies between immune checkpoint inhibition and ADCs, and there are other mAb + maytansine ADCs to test this mechanism against such as Mirvetuxemab Soravtansine which has shown promise against ovarian cancer; the base mAb of this ADC doesn't seem to have any effect alone, whereas naked Trastuzumab itself seems to elicit an immunological response.Unknownhttps://www.blogger.com/profile/18054891182346054370noreply@blogger.comtag:blogger.com,1999:blog-6821948329541212415.post-4591590454201845432015-12-02T17:09:29.127-05:002015-12-02T17:09:29.127-05:00Most likely not. The paper only mentioned that T-D...Most likely not. The paper only mentioned that T-DM1 is used against Herceptin resistant cancers. David Usharaulihttps://www.blogger.com/profile/02668672470276307921noreply@blogger.comtag:blogger.com,1999:blog-6821948329541212415.post-75429147469410258852015-12-02T16:10:31.624-05:002015-12-02T16:10:31.624-05:00Does the same effect occur when the naked anti-bod...Does the same effect occur when the naked anti-body Herceptin is used?Unknownhttps://www.blogger.com/profile/18054891182346054370noreply@blogger.com