한빛사 논문
Yujin Kim,†[a,b,c] Sukmo Kang,†[b,c] Hocheol Shin,[a,b,c] Taewoo Kim,[a,b,c] Byeongjun Yu,[a,b,c] Jinjoo Kim,[a,b,c] Dohyun Yoo[a,b,c] and Sangyong Jon*[a,b,c]
[a]Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea.
[b]KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea.
[c]Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea.
[†]These authors contributed equally to this work.
*Corresponding author
Abstract
Cancer nanovaccines that use nanomaterials as antigens and/or adjuvant‐delivering carriers can induce tumor antigen‐specific T cell immunity and have shown potential as therapeutic modalities in in vivo animal models. Moreover, the addition of immune checkpoint blockade (ICB) immunotherapy to cancer nanovaccines can further potentiate the antitumor efficacy of the latter. However, little effort has been made to develop an optimal treatment regimen based on treatment sequence and the timing of each modality. The present study describes a small lipid nanoparticle (SLNP)‐based nanovaccine platform and a new combination treatment regimen. Tumor antigen‐displaying, CpG adjuvant‐embedded SLNPs (OVAPEP‐SLNP@CpG) were prepared from biocompatible phospholipids and a cationic cholesterol derivative. The resulting nanovaccine showed highly potent antitumor efficacy in both prophylactic and therapeutic E.G7 tumor models. However, this vaccine simultaneously induced T cell exhaustion by elevating PD‐L1 expression, leading to tumor recurrence. Thus, the nanovaccine was combined with simultaneous anti‐PD‐1 antibody treatment, but the therapeutic efficacy of this regimen was comparable to that of the nanovaccine alone. Finally, mice that showed a good therapeutic response after the first cycle of immunization with the nanovaccine underwent a second cycle of immunization together with anti‐PD‐1 therapy, resulting in effective suppression of tumor relapse. These findings suggest that the antitumor efficacy of combinations of nanovaccines with ICB therapy is dependent on treatment sequence and the timing of each modality.
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