CARG-2020 / CaroGen - LARVOL DELTA

CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer. (PubMed, Sci Rep) - "Administration of CARG-2020 resulted in increased accumulation of CD8+ T lymphocytes in the tumors, and depletion of these T cells results in poor tumor regression mediated by CARG-2020. Overall, our study shows a broad-spectrum efficacy of CARG-2020 in solid tumors and demonstrates the potential of CARG-2020 to be developed as a clinical candidate for the treatment of multiple human cancers that are surgically accessible."

IO biomarker • Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • IL12A • IL17A • IL17RA

Virus like vesicle based multivalent immunotherapy for solid tumors (SITC 2024) - "Conclusions The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy. Ethics Approval All mice were kept at a specific-pathogen-free facility, and all mouse experiments were approved by the Institutional Animal Care and Use Committee at UConn Health.Download figure Open in new tab Download powerpoint Abstract 1338 Figure 1 Graphical abstract"

IO biomarker • Colorectal Cancer • Liver Cancer • Oncology • Solid Tumor • IL12A • IL17A • IL17RA

Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence. (PubMed, Acta Pharm Sin B) - "Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy."

IO biomarker • Journal • Immunology • Oncology • IL12A • IL17A • IL17RA

Cancer immunotherapy modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence: Study (Science X) - "Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation...The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory....CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation."

Preclinical • Solid Tumor

Immune modulation of innate and adaptive responses restores immune surveillance and establishes anti-tumor immunological memory. (PubMed, Cancer Immunol Res) - "To achieve this, we developed CARG-2020, a genetically modified virus-like vesicle (VLV) that is a self-amplifying RNA with oncolytic capacity and encodes immune regulatory genes...Furthermore, we demonstrated that this therapeutic approach provided tumor-specific and long-term protection against the establishment of new tumors. Our results provide rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients to enhance anti-tumor responses and prevent recurrence."

Journal • Immune Modulation • Immunology • Oncology • Ovarian Cancer • Solid Tumor • CD8 • IL12A • IL17A • IL17RA

Immune modulation of innate and adaptive responses by CARG-2020 restore immunosurveillance and establish anti-tumoral immunological memory (SGO 2023) - No abstract available

Immune Modulation • Immunology • Oncology

Cancer immunotherapy with oncolytic enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways (IMMUNOLOGY 2022) - "Mechanistically, CARG-2020 potently activates Th1-armed immunity in primary tumors and the spleen, and inhibits the expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence in mice and extending their survival makes it a promising candidate for use in human cancer immunotherapy."

IO biomarker • Immune Modulation • Immunology • Inflammation • Oncology • IL12A • IL17A • IL17RA

CARG-2020 a novel immunemodulatory approach to prevent recurrent ovarian cancer (AACR 2022) - "We report the successful anti-tumoral effect of CARG-2020 by modulating the immune response in a syngeneic mouse model of recurrent ovarian cancer. CARG-2020, by enhancing the expression of IL-12 and blocking IL-17 and PD-L1, provided a long-term protection associated with the expansion of cytolytic effector memory CD8+T cells, which in addition to its antitumoral effect, provides protection against recurrent disease. Our results provide rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients."

IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • CD44 • CD8 • IL12A

[VIRTUAL] CARG-2020, an oncolytic artificial virus co-delivering three immunomodulators, to regress and cure established tumors in mice. (ASCO 2021) - "As an oncolytic RNA replicon, AVIDIO platform-derived CARG-2020 encodes IL-12, dn-IL-17RA and PD-L1 shRNAs which are expressed concurrently within the same vector . CARG-2020 modulates IL-12, IL-17RA and PD-L1 signaling, and exerts broad immune modulation in tumor microenvironment . Treatment with CARG-2020 eliminates the majority of grafted large tumors in mice, and is effective against both primary and distal tumors ."

IO biomarker • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD8 • CXCL1 • IL12A • IL17A

[VIRTUAL] CARG-2020 artificial oncolytic virus delivering three immune-modulators prevents tumor recurrence in a syngeneic model of ovarian cancer (AACR 2021) - "CARG-2020 is able to prevent the establishment of recurrent disease in a syngeneic mouse model of recurrent ovarian cancer. Our results provide rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients."

Oncolytic virus • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • IL12A • PD-L1