Hybrid Membrane Nanovaccines Combined with Immune Checkpoint Blockade to Enhance Cancer Immunotherapy

Abstract

Purpose Cancer vaccines are a promising therapeutic approach in cancer immunotherapy and can inhibit tumor growth and prevent tumor recurrence and metastasis by activating a sustained antitumor immunoprotective effect. However, the therapeutic effect of cancer vaccines is severely weakened by the low immunogenicity of cancer antigens and the immunosuppressive microenvironment in tumor tissues. Methods Here, we report a novel hybrid membrane nanovaccine, composed of mesoporous silica nanoparticle as a delivery carrier, hybrid cell membranes obtained from dendritic cells and cancer cells, and R837 as an immune adjuvant (R837@HM-NPs). We investigated the anti-tumor, tumor recurrence and metastasis prevention abilities of R837@HM-NPs and their mechanisms of action through a series of in vivo and ex vivo experiments. Results R837@HM-NPs not only provide effective antigenic stimulation but are also a durable supply of the immune adjuvant R837. In addition, R837@HM-NPs promote antigen endocytosis into dendritic cells via various receptor-mediated pathways. Compared with HM-NPs or R837@HM-NPs, R837@HM-NPs in combination with an immune checkpoint blockade showed stronger antitumor immune responses in inhibiting tumor growth, thus eliminating established tumors, and rejecting re-challenged tumors by regulating the immunosuppressive microenvironment and immunological memory effect. Conclusion These findings suggest that the hybrid membrane nanovaccine in combination with immune checkpoint blockade is a powerful strategy to enhance antitumor immunotherapy without concerns of systemic toxicity.

Engineered biological nanoparticles as nanotherapeutics for tumor immunomodulation

“…Tumor cell membrane-coated nanoparticles are at the forefront of this research, with studies demonstrating their ability to mimic the antigenic profile of tumors and stimulate specific immune responses. [158][159][160] These biomimetic platforms have been engineered to deliver Risk -averse regulatory environment Unmet needs in hematological malignancies after patients fail CAR-T cell therapy costimulatory signals, activate antigen-presenting cells, and elicit robust CD8 + T-cell responses, showing promise in preclinical and clinical settings. Integrating these nanoparticles with other therapeutic modalities, such as photodynamic, sonodynamic, and photothermal therapies, further amplifies their immunomodulatory effects.…”

Multifunctional nanoparticle for cancer therapy

“…Based on the delivery capability of a cell membrane, multifunctional hybrid cell membrane nanoparticles are codelivered with functional materials by electrostatic interaction. [333][334][335] Initially, the cancer cell membrane could be fused with the bacteria membrane by electrostatic interaction to encapsulate photothermal nanoparticle. For example, Guo et al developed a multifunctional nanoparticle Fe 3 O 4 /MnO 2 /MM/EM/D based on the MCF-7 breast cancer cell membrane (MM) and Escherichia coli membrane (EM).…”

“…A hybrid cell membrane is prepared by fusing various cell membranes through electrostatic interactions, which contain various surface membrane protein markers from different cells. Based on the delivery capability of a cell membrane, multifunctional hybrid cell membrane nanoparticles are codelivered with functional materials by electrostatic interaction 333–335 . Initially, the cancer cell membrane could be fused with the bacteria membrane by electrostatic interaction to encapsulate photothermal nanoparticle.…”

Recent advances in nanomedicine preparative methods and their therapeutic potential for colorectal cancer: a critical review

“…A nanovaccine that comprises certain tumor antigens like carcinoembryonic antigen (CEA) or mucin 1 (MUC1) that demonstrates a response resistance to sickness and tumor progression has demonstrated promising outcomes in clinical models. Additionally, Toll-like receptor agonists or NPs containing internal components may be used in nanovaccines and nanoimmunotherapies to enhance immunity and antigen presentation ( 179 ). Although clinical studies and the development of nanovaccine and nanoimmunotherapy for CRC are still in their early phases, they have the potential to enhance the immune system’s performance in CRC patients ( 180 ).…”