Abstract P006: Intratumoral electroporation of IL-12 and SARS-Cov-2 spike plasmids drives a coordinated vaccine response and elicits robust anti-tumor immunity

Abstract

Abstract Despite extensive clinical evidence on the efficacy and safety of SARS-CoV-2 vaccines, there remains a paucity of data on their effectiveness in cancer patients who are actively receiving antineoplastic therapeutics. A recent study demonstrated only ~30% of cancer patients had positive serologic test following 2 doses of FDA-authorized SARS-CoV-2 vaccines, in contrast to ~80% positivity rate in healthy individuals, regardless of the age. Therefore, further investigation into novel approaches to boost immune response to SARS-CoV-2 vaccines in cancer patients is required. Our previous preclinical and clinical studies have established intratumoral IL-12 plasmid (TAVO) electroporation (EP) induces localized expression of IL-12p70, converting immune-excluded tumors into inflamed immunogenic lesions, thereby generating objective responses in both treated and untreated, distant tumors. Based on the enhancement of immunotherapy efficacy by IL-12, we leveraged the flexibility of our DNA plasmid-EP platform to express SARS-CoV-2 spike protein in addition to IL-12 (CORVax12) as an intratumoral vaccine candidate which we hypothesized could not only drive anti-SARS-CoV-2 immune responses but also generate a productive anti-tumor response. Naïve mice were vaccinated via intradermal injection of SARS-CoV-2 spike plasmid followed immediately by EP with or without plasmid-encoded mIL-12 on days 1 and 21. Longitudinal serum samples were collected to interrogate virus-specific cellular responses as well anti-spike IgG antibody. A surrogate viral neutralization test (sVNT) assessed serum blockade of soluble human ACE2 binding to immobilized SARS-CoV-2 spike. Our data demonstrated that intradermally electroporated CORVax12 elicits significantly higher anti-SARS-CoV-2 spike IgG antibodies and neutralization when compared with EP of SARS-CoV-2 spike alone. Next, we asked if improved SARS-CoV-2 immune response may be observed when CORVax12 is incorporated into intratumoral EP in single-tumor bearing mice. CORVax12 robustly inhibited tumor growth, induced high percentages of germinal-center B cells and class switched B cells in tumor draining lymph nodes, and generated high of anti-spike IgG and neutralization antibodies. To further investigate systemic effects of this combination, we continued with contralateral tumor mice models. In both CT26 and B16-F10 tumor models, CORVax12 intratumoral EP induced strong systemic anti-tumor responses similar to IL-12 EP alone while also producing high serum levels of anti-SARS-CoV-2 spike IgG and neutralization antibodies. Critically, this anti-viral immunity did not limit this IL-12-based intratumoral anti-tumor therapy. In summary, our preclinical data indicates that intratumoral EP of CORVax12 can induce IgG responses to SARS-CoV-2 spike as well as apparent viral neutralizing activity all while maintaining local and systemic anti-tumor effects expected from TAVO Treatment. This combined intratumoral therapy represents a novel strategy to address both tumor burden and anti-SARS-CoV-2 immunity in patients with cancer. Citation Format: Mia Han, Jack Y. Lee, Vincent Wu, Kurt Sakurada, Bianca Nguyen, David A. Canton, Christopher G. Twitty. Intratumoral electroporation of IL-12 and SARS-Cov-2 spike plasmids drives a coordinated vaccine response and elicits robust anti-tumor immunity [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P006.