Dr Alvero on Antitumor Immunological Memory in Ovarian Cancer Models

Ayesha Alvero, MD, MSc, professor, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, discusses findings from a preclinical study investigating the antitumor effects and recurrence prevention abilities of a virus-like vesicle thought to establish immunological memory in mouse models with ovarian cancer.

Dr Alvero on the Mechanism of Action of CARG-2020 in Ovarian Cancer Cells

This study aimed to develop an immunotherapy to prevent ovarian cancer recurrence using the novel virus-like vesicle CARG-2020 in ovarian cancer syngeneic mouse models. The study investigators determined that to prevent recurrent disease with the immune system, the immune system needed the capability to recognize and remember the tumors, Alvero says. The investigators hypothesized that they could establish immunological memory by simultaneously activating both the innate and the adaptive arms of the immune system, to enhance antigen presentation and promote cytotoxic T-cell expansion, respectively, Alvero explains.

CARG-2020 can deliver 3 immune modulators: IL-12, the IL-17 receptor agonist IL-17R, and shRNA-mediated PD-L1 silencing, Alvero notes. IL-12 is thought to promote a cytotoxic T-cell response, prevent the activity of regulatory T cells, and improve antigen presentation. IL-17R is expected to prevent myeloid-derived suppressor cell (MDSC) recruitment and cancer cell growth, thereby inhibiting immunosuppressive cell expansion. shRNA inhibits the PD-L1 immune checkpoint.

Dr Alvero on the Efficacy of CARG-2020 in Ovarian Cancer Models

An in vitro portion of this study found that CARG-2020 is oncolytic and able to express its cargo. The subsequent in vivo part of this study found that CARG-2020 induced tumor regression and improved overall survival in mouse models that received ovarian cancer cells, Alvero says. When the investigators rechallenged the same mice with the cancer cells to mimic recurrent disease, many of the tumor cells did not survive, Alvero emphasizes. These findings indicate the ability of CARG-2020 to establish specific antitumor immunological memory, Alvero explains. Specifically, the investigators found that CARG-2020 promotes CD8 memory T-cell expansion, prevents MDSC expansion, prevents M2 macs expansion, and promotes M1 macrophage expansion.

Disclosures: Dr Alvero reports scientific advisory board participation with the Carogen Corporation.