<br>针对 KitK641E 突变黑色素瘤的混合仿生纳米疫苗（HBNV）的制造和功能验证,Bioactive Materials

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针对 KitK641E 突变黑色素瘤的混合仿生纳米疫苗（HBNV）的制造和功能验证
Bioactive Materials ( IF 18.0 ) Pub Date : 2024-12-27 , DOI: 10.1016/j.bioactmat.2024.12.023
Kishwor Poudel ₁ , Zhenyu Ji ₁ , Ching-Ni Njauw ₁ , Anpuchchelvi Rajadurai ₁ , Brijesh Bhayana ₁ , Ryan J Sullivan ₂ , Jong Oh Kim ₃ , Hensin Tsao _{1,

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Affiliation

癌症纳米疫苗通过整合有效免疫刺激所必需的所有元素，有望实现个性化、精确性和柔韧性。有效的免疫反应需要抗原呈递细胞（APC）、肿瘤细胞和免疫细胞之间的通讯和相互作用，以刺激、延伸和分化抗原特异性和非特异性抗肿瘤免疫细胞。纳米药物的多功能性可以适应从免疫关键参与者（即 APC 和肿瘤细胞）提供免疫辅助有效载荷和抗原。对于对小分子 c-KIT 和免疫检查点抑制剂耐药的不太常见但更具破坏性的 KIT 突变肢端和粘膜黑色素瘤，新型癌症药物的当务之急尤为紧迫。为了克服这一挑战，我们成功设计了基于纳米技术的混合仿生纳米疫苗（HBNV），该疫苗由来自融合细胞（APC 和肿瘤细胞）的膜蛋白（激活免疫和归巢/靶向配体到肿瘤微环境（TME）和淋巴器官）和免疫佐剂组成。这些 HBNVs 有效地内化到靶细胞中，通过抗原和佐剂协助 APCs 成熟，激活抗肿瘤细胞因子的释放/抑制免疫抑制细胞因子的释放，对 TME 和淋巴结表现出同型作用，激活抗肿瘤免疫细胞/下调免疫抑制免疫细胞，重编程肿瘤微环境，并显示出成功的抗肿瘤治疗和预防作用。

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Fabrication and functional validation of a hybrid biomimetic nanovaccine (HBNV) against KitK641E-mutant melanoma

Cancer nanovaccines hold the promise for personalization, precision, and pliability by integrating all the elements essential for effective immune stimulation. An effective immune response requires communication and interplay between antigen-presenting cells (APCs), tumor cells, and immune cells to stimulate, extend, and differentiate antigen-specific and non-specific anti-tumor immune cells. The versatility of nanomedicine can be adapted to deliver both immunoadjuvant payloads and antigens from the key players in immunity (i.e., APCs and tumor cells). The imperative for novel cancer medicine is particularly pressing for less common but more devastating KIT-mutated acral and mucosal melanomas that are resistant to small molecule c-kit and immune checkpoint inhibitors. To overcome this challenge, we successfully engineered nanotechnology-enabled hybrid biomimetic nanovaccine (HBNV) comprised of membrane proteins (antigens to activate immunity and homing/targeting ligand to tumor microenvironment (TME) and lymphoid organs) from fused cells (of APCs and tumor cells) and immunoadjuvant. These HBNVs are efficiently internalized to the target cells, assisted in the maturation of APCs via antigens and adjuvant, activated the release of anti-tumor cytokines/inhibited the release of immunosuppressive cytokine, showed a homotypic effect on TME and lymph nodes, activated the anti-tumor immune cells/downregulated the immunosuppressive immune cells, reprogram the tumor microenvironment, and showed successful anti-tumor therapeutic and prophylactic effects.

更新日期：2024-12-27

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