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. 2021 Sep 30;9(9):e002569. doi: 10.1136/jitc-2021-002569

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© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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Working model of heat-inactivated vaccinia as a stronger inducer of anti-tumor innate immunity especially in distant tumors compared with live OV-GM. (A) Schematic of induction of innate immunity by IT delivery of heat-inactivated vaccinia vs. live oncolytic vaccinia in both injected and non-injected distant tumors (created with biorender.com). (B) Comparison of immune activation by heat-inactivated vaccinia vs. live oncolytic vaccinia. IT delivery of heat-inactivated vaccinia induces (i) higher levels of type I IFN than live oncolytic vaccinia due to activation of the cGAS/STING-mediated cytosolic DNA-sensing pathway; (ii) stronger T cell priming in TDLNs and spleen; and (iii) more activated T cells, which then migrate to the distant tumors resulting in enhanced abscopal tumor cell killing and eventually tumor regression through the induction of a stronger innate immunity.