Recombinant adeno-associated viruses (rAAV2) facilitate the intraperitoneal gene delivery to cancer cells

Abstract

Abstract. Peritoneal dissemination of cancer cells is characteristic of advanced stages of ovarian, breast and lung cancers, and is associated with poor patient survival. the presence of cancer cells in effusions complicates treatment protocols, while cell eradication is seriously limited. one of the novel options available is cancer gene therapy with recombinant adeno-associated viruses. this combination represents the most promising gene delivery vehicles to neoplasmatic cells within serosal cavities due to their unique properties that include the ability to infect proliferating cells of broad host range, as well as the potential of long-term expression. recombinant infectious adeno-associated virus serotype 2 particles (rAAV2) were produced in a helper-free system using an AAV-293 packaging cell line, and quantitatively analyzed by real-time Pcr. Balb/c mice intraperitoneally pre-injected with l1 cancer cells were treated with different doses of rAAV2. subsequently, the mice were sacrificed and intraperitoneal effusions were analyzed for rAAV presence and rAAV/β-galactosidase (lacZ) vector efficiency in order to infect cancer cells within the peritoneal cavity. We reported an efficient infection of L1 cancer cells disseminated into the peritoneal cavity by rAAV2. the expression of reporter genes (GFP and LacZ) attributable to the rAAV cell uptake was closely dependent on an applied multiplicity of infection ratio (MoI). the highest infection efficiency was observed at a MOI of 50 and 200. Our study confirmed the ability of adeno-associated viruses to facilitate gene transferability to cancer cells disseminated in the serosal cavity, as well as the potential usefulness of these viruses as a new approach in cancer gene therapy.

Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator

“…46 Although AAV can be an effective vector for gene delivery in many types of animal diseases, there is currently no evidence of which cell types may be infected by peritoneal injections. Maciej et al 47 reported that AAV could facilitate gene transferability to cancer cells disseminated in the serosal cavity. Epithelial cells have been reported to be the first infective target of AAV-mediated cancer gene therapy after peritoneal injection.…”

“…Epithelial cells have been reported to be the first infective target of AAV-mediated cancer gene therapy after peritoneal injection. 47 We hypothesize that AAV-IL-12 infected intraperitoneal tumor cells or peritoneal lining cells and mesothelial cells in our model.…”

Designing cytochrome P450 enzymes for use in cancer gene therapy

“…In the realm of cancer gene therapy, various strategies have been explored, including the transfer of tumor suppressor genes, suicide genes, enzyme/pro-drug approach (like GDEPT), inhibition of dominant oncogenes, immunomodulation approaches, and expression of molecules affecting angiogenesis, tumor invasion, and metastasis ( Seth, 2005 ). The use of recombinant adeno-associated viruses (rAAV2) for intraperitoneal gene delivery to cancer cells, besides bacteria-mediated cancer gene therapy and the development of new vector systems, exemplifies the continuous progress and advanced strategies being employed in this field ( Cao et al, 2010 ; Malecki et al, 2010 ; Zu and Gao, 2021 ; Bulcha et al, 2021 ; Thoidingjam et al, 2023 ). Of utmost importance remains bridging the gap between research and clinical application for successful clinical translation of recent advances.…”