An intratumoural cytotopic immunotherapy approach in a syngeneic murine model of prostate cancer
BAUS ePoster online library. Elhage O.
Jun 26, 2018; 211333
Mr. Oussama Elhage
Mr. Oussama Elhage
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Introduction: The immunosuppressive prostate cancer microenvironment renders most infiltrating effector immune cells anergic or regulatory. Immunotherapeutic agents localised to the prostate can break this immune-tolerance leading to greater efficacy and less toxicity than systemically-administered drugs. We showed previously that cytotopic modification of interleukin-15 can activate NK and CD8+ T-cells in the presence of prostate cancer cells. We now used this cyto-IL-15 and two immuno-checkpoint blocking antibodies, which exhibited anti-tumour response in clinical trials, modified in a similar approach.

Methods: IL-15 and antibodies were modified by conjugation to a molecule that enables them to adhere to cell membranes (patents pending), and thus localize to any potential site of injection. The cytotopically modified IL-15 and antibodies was injected intratumourally either alone (cyto-IL-15 or cyto-abs) or in combination (cyto-combo) in subcutaneous TRAMP C2 prostate tumours in C57BL/6 mice and compared with their non-modified equivalents.

Results: Intratumoural injection of cyto-IL15, combo or cyto-combo significantly delayed tumour growth at day 14 post-treatment by 45-50%. However, only cyto-IL15 and cyto-combo significantly increased median survival after treatment to 28 (p < 0.05) and 24 days (p < 0.05) respectively, compared with 17 days in the control group. Non-modified IL15 or antibodies alone had no effect on tumour growth or survival.

Conclusion: We have demonstrated that cytotopically modified immunotherapeutic agents can lead to tumour growth delay in an in vivo murine model of prostate cancer, induce tumour cell death and increase mouse survival. This appears to be a promising novel approach for prostate cancer immunotherapy.
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