(If someone can tell me how to host or post the article, I'll try!)
Taken from article:
Highlights
• Tumor-specific T cells are necessary but not sufficient for therapeutic efficacy
• IV vaccination promotes tumor regression by remodeling the TME
• Systemic IFN-I following IV vaccination alters intratumoral Chil3+ monocytes
• Enrichment of human homologs of Chil3+ monocytes is associated with worse outcomes
Limitations
There are several limitations to this study. First, the key observations were performed in murine tumor models that may not accurately reflect the tumor immune microenvironment in humans. Key features including tumor architecture, vascularization, growth rate, and immune infiltrate may differ in patients when compared to a transplanted tumor in mice. Second, we have used two murine tumor models (MC38 and TC-1) that are both immune-inflamed tumors. As such, the findings of this study may not model immune-excluded or immune-desert tumors. Third, although we have performed experiments using IFNAR1 blocking antibodies to show that vaccine-induced IFN-I can modulate the Chil3+ monocytes in the tumor, we did not provide direct evidence that Chil3+ monocytes are responsible for suppressing the antigen-specific CD8+ T cells. Finally, the human TCGA data included in this study highlight LGG and ccRCC, two cancer indications where the enrichment of HuChil3 monocyte genes is associated with worse survival compared to pan monocyte genes; this observation may not be generalizable to all tumors. Nevertheless, despite these limitations we believe these data provide a translatable approach for using innate stimulation by intravenous vaccination to potentially improve T cell function in tumors that express such inhibitory profiles.
Declaration of interests
A.S.I., G.M.L., and R.A.S. are listed as inventors on patents describing polymer-based vaccines. A.S.I. and G.M.L. are employees of Vaccitech North America, which is commercializing polymer-based drug delivery technologies for immunotherapeutic applications. F.B. and S.M. are employees of Genentech, a member of the Roche group, which develops and markets drugs for profit
TheReigningSupreme t1_ivwrj0s wrote
Reply to Experimental cancer vaccine shows promise in animal studies by BoundariesAreFun
(If someone can tell me how to host or post the article, I'll try!)
Taken from article:
Highlights
• Tumor-specific T cells are necessary but not sufficient for therapeutic efficacy
• IV vaccination promotes tumor regression by remodeling the TME
• Systemic IFN-I following IV vaccination alters intratumoral Chil3+ monocytes
• Enrichment of human homologs of Chil3+ monocytes is associated with worse outcomes
Limitations
There are several limitations to this study. First, the key observations were performed in murine tumor models that may not accurately reflect the tumor immune microenvironment in humans. Key features including tumor architecture, vascularization, growth rate, and immune infiltrate may differ in patients when compared to a transplanted tumor in mice. Second, we have used two murine tumor models (MC38 and TC-1) that are both immune-inflamed tumors. As such, the findings of this study may not model immune-excluded or immune-desert tumors. Third, although we have performed experiments using IFNAR1 blocking antibodies to show that vaccine-induced IFN-I can modulate the Chil3+ monocytes in the tumor, we did not provide direct evidence that Chil3+ monocytes are responsible for suppressing the antigen-specific CD8+ T cells. Finally, the human TCGA data included in this study highlight LGG and ccRCC, two cancer indications where the enrichment of HuChil3 monocyte genes is associated with worse survival compared to pan monocyte genes; this observation may not be generalizable to all tumors. Nevertheless, despite these limitations we believe these data provide a translatable approach for using innate stimulation by intravenous vaccination to potentially improve T cell function in tumors that express such inhibitory profiles.
Declaration of interests
A.S.I., G.M.L., and R.A.S. are listed as inventors on patents describing polymer-based vaccines. A.S.I. and G.M.L. are employees of Vaccitech North America, which is commercializing polymer-based drug delivery technologies for immunotherapeutic applications. F.B. and S.M. are employees of Genentech, a member of the Roche group, which develops and markets drugs for profit