Wouters Roxanne, Westrøm Sara, Vankerckhoven Ann, Thirion Gitte, Ceusters Jolien, Claes Sandra, Schols Dominique, Bønsdorff Tina B, Vergote Ignace, Coosemans An
Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, KU Leuven, 3000 Leuven, Belgium.
Oncoinvent AS, 0484 Oslo, Norway.
Pharmaceutics. 2022 Mar 22;14(4):687. doi: 10.3390/pharmaceutics14040687.
Novel treatment strategies are needed to provide a better prognosis for ovarian cancer. For this purpose, the current study was designed to evaluate the effects of different types of particle drug carriers on tumor response and on the tumor immune microenvironment (TME) after intraperitoneal (IP) administration in a murine tumor model. Mice with ID8-fLuc ovarian cancer were injected IP with pegylated liposomes, hydroxyapatite, polystyrene, poly(lactic-co-glycolic acid) (PLGA) and calcium carbonate (CaCO) microparticles to evaluate the effect of the candidate carriers without drugs. Our results show that several types of microparticle drug carriers caused hyperproliferation of the tumor when injected IP, as reflected in a reduced survival or an accelerated onset of ascites. Alterations of the product formulation of CaCO microparticles could result in less hyperproliferation. The hyperproliferation caused by CaCO and PLGA was largely driven by a strong innate immune suppression. A combination with chemotherapy was not able to sufficiently counteract the tumor progression caused by the drug carriers. This research points towards the importance of evaluating a drug carrier before using it in a therapeutic setting, since drug carriers themselves can detrimentally influence tumor progression and immune status of the TME. However, it remains to be determined whether the hyperproliferation in this model will be of relevance in other cancer models or in humans.
需要新的治疗策略来改善卵巢癌的预后。为此，本研究旨在评估在小鼠肿瘤模型中腹腔内（IP）给药后，不同类型的颗粒药物载体对肿瘤反应和肿瘤免疫微环境（TME）的影响。将携带ID8-fLuc卵巢癌的小鼠腹腔内注射聚乙二醇化脂质体、羟基磷灰石、聚苯乙烯、聚乳酸-羟基乙酸共聚物（PLGA）和碳酸钙（CaCO）微粒，以评估不含药物的候选载体的效果。我们的结果表明，几种类型的微粒药物载体腹腔内注射后会导致肿瘤过度增殖，表现为生存率降低或腹水出现加速。CaCO微粒产品配方的改变可能会减少过度增殖。CaCO和PLGA引起的过度增殖在很大程度上是由强烈的先天性免疫抑制驱动的。与化疗联合使用并不能充分抵消药物载体引起的肿瘤进展。这项研究指出了在治疗环境中使用药物载体之前评估其重要性，因为药物载体本身可能会对肿瘤进展和TME的免疫状态产生不利影响。然而，该模型中的过度增殖在其他癌症模型或人类中是否具有相关性仍有待确定。
