Details

Autor(en) / Beteiligte

• Shakiba, Yasmin
• Vorobyev, Pavel O.
• Yusubalieva, Gaukhar M.
• Kochetkov, Dmitry V.
• Zajtseva, Ksenia V.
• Valikhov, Marat P.
• Kalsin, Vladimir A.
• Zabozlaev, Fedor G.
• Semkina, Alevtina S.
• Troitskiy, Alexander V.
• Baklaushev, Vladimir P.
• Chumakov, Peter M.
• Lipatova, Anastasia V.

Titel

Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response

Ist Teil von

• Molecular therapy. Oncolytics, 2023-06, Vol.29, p.158-168

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• We developed recombinant variants of oncolytic vaccinia virus LIVP strain expressing interleukin-15 (IL-15) or its receptor subunit alpha (IL-15Rα) to stimulate IL-15-dependent immune cells. We evaluated their oncolytic activity either alone or in combination with each other in vitro and in vivo using the murine CT26 colon carcinoma and 4T1 breast carcinoma models. We demonstrated that the admixture of these recombinant variants could promote the generation of the IL-15/IL-15Rα complex. In vitro studies indicated that 4T1 breast cancer cells were more susceptible to the developed recombinant viruses. In vivo studies showed significant survival benefits and tumor regression in 4T1 breast cancer syngeneic mice that received a combination of LIVP-IL15-RFP with LIVP-IL15Ra-RFP. Histological analysis showed recruited lymphocytes at the tumor region, while no harmful effects to the liver or spleen of the animals were detected. Evaluating tumor-infiltrated lymphocytes represented profound activation of cytotoxic T cells and macrophages in mice receiving combination therapy. Thus, our experiments showed superior oncolytic effectiveness of simultaneous injection of LIVP-IL15-RFP and LIVP-IL15Ra-RFP in breast cancer-bearing mice. The combined therapy by these recombinant variants represents a potent and versatile approach for developing new immunotherapies for breast cancer. [Display omitted] Baklaushev and colleagues developed vaccinia virus strains expressing IL-15 or its receptor IL-15Rα and evaluated in vivo. The results showed a significant increase in survival rate and tumor regression in 4T1 tumor-bearing mice that received combination therapy of VV-IL15 with VV-IL15-Ra associated with enhanced tumor-infiltrated lymphocytes.