RE:RE:CAR-T updateJuly 05, 2023 - Genetic Engineering & Biotechnology News (GEN)
Vaccine boosts CAR T cell therapy for solid tumors
“Mechanistically, we found that the enhanced production of IFN-γ by vaccine-boosted CAR T cells was a major contributor to AS” the team noted. “Vaccine-boosted CAR T promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited the priming of endogenous anti-tumor T cells.” The activated DCs in the tumor in turn secrete IL-12 that, together with the autocrine effect of IFN-γ, enhanced CAR T cell anti-tumor activity, “leading to pronounced endogenous T cell priming and induction of enhanced effector programs in endogenous T cells that infiltrate tumors.”
https://www.genengnews.com/topics/cancer/vaccine-boosts-car-t-cell-therapy-for-solid-tumors/
July 05, 2023 - Journal Cell - Vaccine-boosted CAR T promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited the priming of endogenous anti-tumor T cells.
Vaccine boosting of CAR T cells triggers the engagement of the endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted CAR T promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited the priming of endogenous anti-tumor T cells.
https://www.cell.com/cell/fulltext/S0092-8674(23)00642-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867423006426%3Fshowall%3Dtrue
February 2021 - Canada-based Oncolytics Biotech showing that its oncolytic virus arms CAR-T cells to attack solid tumors
https://www.fiercebiotech.com/research/oncolytics-bio-eyes-car-t-combo-virus-for-solid-tumors-back-promising-mice-data
April 2022 - Oncolytic viruses (OVs) encoding a variety of transgenes have been evaluated as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)-modified T cells in the solid tumor microenvironment (TME). Here, using systemically delivered OVs and CAR T cells in immunocompetent mouse models, we have defined a mechanism by which OVs can potentiate CAR T cell efficacy against solid tumor models of melanoma and glioma. We show that stimulation of the native T cell receptor (TCR) with viral or virally encoded epitopes gives rise to enhanced proliferation, CAR-directed antitumor function, and distinct memory phenotypes. In vivo expansion of dual-specific (DS) CAR T cells was leveraged by in vitro preloading with oncolytic vesicular stomatitis virus (VSV) or reovirus, allowing for a further in vivo expansion and reactivation of T cells by homologous boosting. This treatment led to prolonged survival of mice with subcutaneous melanoma and intracranial glioma tumors. Human CD19 CAR T cells could also be expanded in vitro with TCR reactivity against viral or virally encoded antigens and was associated with greater CAR-directed cytokine production. Our data highlight the utility of combining OV and CAR T cell therapy and show that stimulation of the native TCR can be exploited to enhance CAR T cell activity and efficacy in mice.
https://pubmed.ncbi.nlm.nih.gov/35417192/