Preclinical Evaluation of LVR01 Attenuated Salmonella as Neoadjuvant Intralesional Therapy in Combination with Chemotherapy for Melanoma Treatment

Salmonella-induced immune response reduces recurrence and tumor dissemination in preclinical melanoma model

“…As we had previously described, intratumoral Salmonella LVR01 monotherapy resulted in tumor growth retardation and prolonged survival in a melanoma-bearing mice model ( Vola et al, 2018 ; Chilibroste et al, 2021 Mónaco et al, 2022 ). In this work we studied the potential of Salmonella immunotherapy in a low burden tumor model, achieved by surgery to remove primary tumors.…”

“…We have recently shown the potential of neoadjuvant Salmonella treatment in animals undergoing chemotherapy, highlighting the relevance of low tumor burden for Salmonella success ( Bascuas et al, 2018 ; Chilibroste et al, 2021 ). In line with this, neoadjuvant LVR01 prolongs animal survival upon surgery to remove high tumor burden in a metastatic 4T1 breast cancer model ( Kramer et al, 2015 ).…”

“…Following retrotranscription, quantitative RT-PCR for Ifng, Tnfa, Il6, Il12, Il18, Cxcl1, Cxcl2, Cxcl9, Cxcl10, Ccl2, Ccl3, Ccl4, Ccl5 and Ccl2 0 mRNA were conducted using QuantiTect® SYBR® Green PCR Kit (Qiagen) in a Rotor-Gene 6000 (Corbett), primer sequences are available under request. This panel was based in our previous work, with modifications ( Chilibroste et al, 2021 ). GAPDH encoding gene Gapdh was used as house-keeping gene.…”

“…We have previously developed LVR01, an attenuated Salmonella enterica serovar Typhimurium, that showed to be safe as vaccine vector in many animal models ( Chabalgoity et al, 2000 ; Petavy et al, 2008 ; Goni et al, 2015 ; Grille et al, 2014 ; Kramer et al, 2015 ; Bascuas et al, 2018 ; Vola et al, 2018 ; Chilibroste et al, 2021 ; Mónaco et al, 2022 ). Besides, it holds great potential as a vaccine vector and tool for cancer immunotherapies ( Chabalgoity et al, 2000 ).…”

“…Furthermore, intratumoral injection of LVR01 together with topical administration of the TLR7 agonist imiquimod retards tumor growth and dissemination and prolongs overall survival through the induction of the expression of pro-inflammatory Th1 cytokines and chemokines in the tumor microenvironment (TME), that resulted in a broad antitumor response in local and distant masses ( Vola et al, 2018 ). Moreover, when using neoadjuvant Salmonella combined with intraperitoneal dacarbazine (DTIC) chemotherapy we found a strong synergistic anti-tumor effect, driven by combination of the DTIC-induced reduction of secondary lymphoid organ cellularity and the activation of cytotoxic cell compartments ( Chilibroste et al, 2021 ). Analogously, lymphoma-bearing mice undergoing CHOP chemotherapy benefit from LVR01 administration, resulting in prolonged overall survival and an improved health status ( Bascuas et al, 2018 ).…”