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Lung cancer has the highest incidence and mortality rate worldwide. Immunotherapy is a universal treatment for lung cancer, but its overall treatment remains a challenge. Tumor immunoediting is a process in which the immune system restricts or promotes tumor development through elimination, equilibrium, and escape to change tumor immunogenicity and obtain an immunosuppressive mechanism to promote disease progression. An increasing number of immunotherapy drugs, including monoclonal antibody-targeting drugs and chimeric antigen (Ag) receptor-modified T cells (CAR-T cells), have been used in clinical therapy. Additionally, cancer vaccine development and new clustered regularly spaced short palindromes (CRISPR)-based combination therapies against cancer open up new avenues for immunotherapy. However, these immunotherapies cause autoimmune induction and non-specific inflammation, with many limitations. The development and study of nanoparticle systems have shown the possibility of localization, pharmacokinetic programming, and immunomodulator co-delivery. Rapid advances in nanotechnology over the past decade have provided a strategic impetus for cancer immunotherapy improvements. Nanotechnology advancements in various aspects, such as virus-like size, high surface–volume ratio, and surface modifications to precisely target specific cell types, can be investigated through cancer vaccine and immunomodulator delivery system development. This review presents the current immunotherapy approaches for lung cancer and emphasizes the current process and prospects of the fusion of cancer immunotherapy, nanotechnology, bioengineering, and drug delivery.
Bade, B. C.; Cruz, C. S. C. Lung cancer 2020. Clin. Chest Med. 2020, 41, 1–24.
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J. Clin. 2018, 68, 394–424.
Chen, Z.; Fillmore, C. M.; Hammerman, P. S.; Kim, C. F.; Wong, K. K. Non-small-cell lung cancers: A heterogeneous set of diseases. Nat. Rev. Cancer 2014, 14, 535–546.
Marx, A.; Chan, J. K. C.; Coindre, J. M.; Detterbeck, F.; Girard, N.; Harris, N. L.; Jaffe, E. S.; Kurrer, M. O.; Marom, E. M.; Moreira, A. L. et al. The 2015 world health organization classification of tumors of the thymus: Continuity and changes. J. Thorac. Oncol. 2015, 10, 1383–1395.
Chen, L.; Chen, F. K.; Li, J. D.; Pu, Y. Z.; Yang, C. H.; Wang, Y.; Lei, Y. J.; Huang, Y. C. CAR-T cell therapy for lung cancer: Potential and perspective. Thorac. Cancer 2022, 13, 889–899.
Osmani, L.; Askin, F.; Gabrielson, E.; Li, Q. K. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin. Cancer Biol. 2018, 52, 103–109.
Qu, J. J.; Mei, Q. H.; Chen, L. J.; Zhou, J. Y. Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): Current status and future perspectives. Cancer Immunol. Immunother. 2021, 70, 619–631.
Villaruz, L. C.; Socinski, M. A. Personalized therapy for non-small-cell lung cancer: Which drug for which patient? Semin. Thorac. Cardiovasc. Surg. 2011, 23, 281–290.
Redondo-Sánchez, D.; Petrova, D.; Rodríguez-Barranco, M.; Fernández-Navarro, P.; Jiménez-Moleón, J. J.; Sánchez, M. J. Socio-economic inequalities in lung cancer outcomes: An overview of systematic reviews. Cancers (Basel) 2022, 14, 398.
Abdalla, A. M. E.; Xiao, L.; Miao, Y.; Huang, L. X.; Fadlallah, G. M.; Gauthier, M.; Ouyang, C. X.; Yang, G. Nanotechnology promotes genetic and functional modifications of therapeutic T cells against cancer. Adv. Sci. (Weinh.) 2020, 7, 1903164.
Reda, M.; Ngamcherdtrakul, W.; Nelson, M. A.; Siriwon, N.; Wang, R. J.; Zaidan, H. Y.; Bejan, D. S.; Reda, S.; Hoang, N. H.; Crumrine, N. A. et al. Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment. Nat. Commun. 2022, 13, 4261.
De Jong, W. H.; Borm, P. J. A. Drug delivery and nanoparticles: Applications and hazards. Int. J. Nanomedicine 2008, 3, 133–149.
Suresh, K.; Naidoo, J.; Lin, C. T.; Danoff, S. Immune checkpoint immunotherapy for non-small cell lung cancer: Benefits and pulmonary toxicities. Chest 2018, 154, 1416–1423.
Zhou, F.; Qiao, M.; Zhou, C. C. The cutting-edge progress of immune-checkpoint blockade in lung cancer. Cell. Mol. Immunol. 2021, 18, 279–293.
Sharma, P.; Siddiqui, B. A.; Anandhan, S.; Yadav, S. S.; Subudhi, S. K.; Gao, J. J.; Goswami, S.; Allison, J. P. The next decade of immune checkpoint therapy. Cancer Discov. 2021, 11, 838–857.
Bagchi, S.; Yuan, R.; Engleman, E. G. Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol. Mech. Dis. 2021, 16, 223–249.
Kubli, S. P.; Berger, T.; Araujo, D. V.; Siu, L. L.; Mak, T. W. Beyond immune checkpoint blockade: Emerging immunological strategies. Nat. Rev. Drug Discov. 2021, 20, 899–919.
Steven, A.; Fisher, S. A.; Robinson, B. W. Immunotherapy for lung cancer. Respirology 2016, 21, 821–833.
Qin, S.; Xu, L. P.; Yi, M.; Yu, S. N.; Wu, K. M.; Luo, S. X. Novel immune checkpoint targets: Moving beyond PD-1 and CTLA-4. Mol. Cancer 2019, 18, 155.
Wang, X.; Guo, G. C.; Guan, H.; Yu, Y.; Lu, J.; Yu, J. M. Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma. J. Exp. Clin. Cancer Res. 2019, 38, 87.
Ribas, A.; Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 2018, 359, 1350–1355
Mok, T. S. K.; Wu, Y. L.; Kudaba, I.; Kowalski, D. M.; Cho, B. C.; Turna, H. Z.; Castro, G.; Srimuninnimit, V.; Laktionov, K. K.; Bondarenko, I. et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial. Lancet 2019, 393, 1819–1830.
Reck, M.; Remon, J.; Hellmann, M. D. First-line immunotherapy for non-small-cell lung cancer. J. Clin. Oncol. 2022, 40, 586–597.
Topalian, S. L.; Taube, J. M.; Anders, R. A.; Pardoll, D. M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 2016, 16, 275–287.
Liu, X. T.; Hogg, G. D.; DeNardo, D. G. Rethinking immune checkpoint blockade: “Beyond the T cell”. J. Immunother. Cancer 2021, 9, e001460.
Benci, J. L.; Johnson, L. R.; Choa, R.; Xu, Y. M.; Qiu, J. Y.; Zhou, Z. L.; Xu, B. H.; Ye, D.; Nathanson, K. L.; June, C. H. et al. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade. Cell 2019, 178, 933–948.e14.
Rowshanravan, B.; Halliday, N.; Sansom, D. M. CTLA-4: A moving target in immunotherapy. Blood 2018, 131, 58–67.
Rudd, C. E.; Taylor, A.; Schneider, H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev. 2009, 229, 12–26.
Yuan, J. D.; Gnjatic, S.; Li, H.; Powel, S.; Gallardo, H. F.; Ritter, E.; Ku, G. Y.; Jungbluth, A. A.; Segal, N. H.; Rasalan, T. S. et al. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc. Natl. Acad. Sci. USA 2008, 105, 20410–20415.
Darvin, P.; Toor, S. M.; Nair, V. S.; Elkord, E. Immune checkpoint inhibitors: Recent progress and potential biomarkers. Exp. Mol. Med. 2018, 50, 1–11.
Kalbasi, A.; Ribas, A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 2020, 20, 25–39.
Marzec, M.; Zhang, Q.; Goradia, A.; Raghunath, P. N.; Liu, X. B.; Paessler, M.; Wang, H. Y.; Wysocka, M.; Cheng, M. G.; Ruggeri, B. A. et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc. Natl. Acad. Sci. USA 2008, 405, 20852–20857.
Larkin, J.; Lao, C. D.; Urba, W. J.; McDermott, D. F.; Horak, C.; Jiang, J.; Wolchok, J. D. Efficacy and safety of nivolumab in patients with BRAF V600 mutant and BRAF wild-type advanced melanoma: A pooled analysis of 4 clinical trials. JAMA Oncol. 2015, 1, 433–440.
Dantoing, E.; Piton, N.; Salaün, M.; Thiberville, L.; Guisier, F. Anti-PD1/PD-L1 immunotherapy for non-small cell lung cancer with actionable oncogenic driver mutations. Int. J. Mol. Sci. 2021, 22, 6288.
Keir, M. E.; Butte, M. J.; Freeman, G. J.; Sharpe, A. H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 2008, 26, 677–704.
Postow, M. A.; Sidlow, R.; Hellmann, M. D. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 2018, 378, 158–168.
Sullivan, R. J.; Weber, J. S. Immune-related toxicities of checkpoint inhibitors: Mechanisms and mitigation strategies. Nat. Rev. Drug Discov. 2022, 21, 495–508.
Morad, G.; Helmink, B. A.; Sharma, P.; Wargo, J. A. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell 2021, 184, 5309–5337.
Bejarano, L.; Jordāo, M. J. C.; Joyce, J. A. Therapeutic targeting of the tumor microenvironment. Cancer Discov. 2021, 11, 933–959.
Petitprez, F.; Meylan, M.; De Reyniès, A.; Sautès-Fridman, C.; Fridman, W. H. The tumor microenvironment in the response to immune checkpoint blockade therapies. Front. Immunol. 2020, 11, 784.
Musetti, S.; Huang, L. Nanoparticle-mediated remodeling of the tumor microenvironment to enhance immunotherapy. ACS Nano 2018, 12, 11740–11755.
Shi, Y.; Van Der Meel, R.; Chen, X. Y.; Lammers, T. The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy. Theranostics 2020, 10, 7921–7924.
Iyer, A. K.; Singh, A.; Ganta, S.; Amiji, M. M. Role of integrated cancer nanomedicine in overcoming drug resistance. Adv. Drug Deliv. Rev. 2013, 65, 1784–1802.
Ramanathan, R. K.; Korn, R. L.; Raghunand, N.; Sachdev, J. C.; Newbold, R. G.; Jameson, G.; Fetterly, G. J.; Prey, J.; Klinz, S. G.; Kim, J. et al. Correlation between ferumoxytol uptake in tumor lesions by MRI and response to nanoliposomal irinotecan in patients with advanced solid tumors: A pilot study. Clin. Cancer Res. 2017, 23, 3638–3648.
Riley, R. S.; June, C. H.; Langer, R.; Mitchell, M. J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug Discov. 2019, 18, 175–196.
Teo, P. Y.; Yang, C.; Whilding, L. M.; Parente-Pereira, A. C.; Maher, J.; George, A. J. T.; Hedrick, J. L.; Yang, Y. Y.; Ghaem-Maghami, S. Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid-functionalized polyethylenimine: Strategies to enhance T cell killing. Adv. Healthc. Mater. 2015, 4, 1180–1189.
Song, W. T.; Shen, L. M.; Wang, Y.; Liu, Q.; Goodwin, T. J.; Li, J. J.; Dorosheva, O.; Liu, T. Z.; Liu, R. H.; Huang, L. Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. Nat. Commun. 2018, 9, 2237.
Lv, M. Z.; Chen, M. X.; Zhang, R.; Zhang, W.; Wang, C. G.; Zhang, Y.; Wei, X. M.; Guan, Y. K.; Liu, J. J.; Feng, K. C. et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res. 2020, 30, 966–979.
Nakamura, T.; Sato, T.; Endo, R.; Sasaki, S.; Takahashi, N.; Sato, Y.; Hyodo, M.; Hayakawa, Y.; Harashima, H. STING agonist loaded lipid nanoparticles overcome anti-PD-1 resistance in melanoma lung metastasis via NK cell activation. J. Immunother. Cancer 2021, 9, e002852.
Cen, D.; Ge, Q. W.; Xie, C. K.; Zheng, Q.; Guo, J. S.; Zhang, Y. Q.; Wang, Y. F.; Li, X.; Gu, Z.; Cai, X. J. ZnS@BSA nanoclusters potentiate efficacy of cancer immunotherapy. Adv. Mater. 2021, 33, 2104037.
Guan, X.; Sun, L. P.; Shen, Y. T.; Jin, F. S.; Bo, X. W.; Zhu, C. Y.; Han, X. X.; Li, X. L.; Chen, Y.; Xu, H. X. et al. Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis. Nat. Commun. 2022, 13, 2834.
Xiao, Y. L.; Chen, J.; Zhou, H.; Zeng, X. D.; Ruan, Z. P.; Pu, Z. Y.; Jiang, X. Y.; Matsui, A.; Zhu, L. L.; Amoozgar, Z. et al. Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy. Nat. Commun. 2022, 13, 758.
Awadasseid, A.; Wu, Y. L.; Tanaka, Y.; Zhang, W. Current Advances in the Development of SARS-CoV-2 Vaccines. Int. J. Biol. Sci. 2021, 17, 8–19.
Li, S. D.; Huang, L. Stealth nanoparticles: High density but sheddable PEG is a key for tumor targeting. J. Control. Release 2010, 145, 178–181.
Zou, Y.; Wei, Y. H.; Sun, Y. P.; Bao, J.; Yao, F. R.; Li, Z. K.; Meng, F. H.; Hu, C. H.; Storm, G.; Zhong, Z. Y. Cyclic RGD-functionalized and disulfide-crosslinked iodine-rich polymersomes as a robust and smart theranostic agent for targeted CT imaging and chemotherapy of tumor. Theranostics 2019, 9, 8061–8072.
Gorabi, A. M.; Ravari, M. S.; Sanaei, M. J.; Davaran, S.; Kesharwani, P.; Sahebkar, A. Immune checkpoint blockade in melanoma: Advantages, shortcomings and emerging roles of the nanoparticles. Int. Immunopharmacol. 2022, 113, 109300.
Granhøj, J. S.; Jensen, A. W. P.; Presti, M.; Met, Ö.; Svane, I. M.; Donia, M. Tumor-infiltrating lymphocytes for adoptive cell therapy: Recent advances, challenges, and future directions. Exp. Opin. Biol. Ther. 2022, 22, 627–641.
Weber, J. S. At the bedside: Adoptive cell therapy for melanoma-clinical development. J. Leukoc. Biol. 2014, 95, 875–882.
Rapoport, A. P.; Stadtmauer, E. A.; Binder-Scholl, G. K.; Goloubeva, O.; Vogl, D. T.; Lacey, S. F.; Badros, A. Z.; Garfall, A.; Weiss, B.; Finklestein, J. et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat. Med. 2015, 21, 914–921.
Rozenbaum, M.; Meir, A.; Aharony, Y.; Itzhaki, O.; Schachter, J.; Bank, I.; Jacoby, E.; Besser, M. J. Gamma-delta CAR-T cells show CAR-directed and independent activity against leukemia. Front. Immunol. 2020, 11, 1347.
Yu, J. X.; Upadhaya, S.; Tatake, R.; Barkalow, F.; Hubbard-Lucey, V. M. Cancer cell therapies: The clinical trial landscape. Nat. Rev. Drug Discov. 2020, 19, 583–584.
D'Aloia, M. M.; Zizzari, I. G.; Sacchetti, B.; Pierelli, L.; Alimandi, M. CAR-T cells: The long and winding road to solid tumors. Cell Death Dis 2018, 9, 282.
Lin, H. L.; Cheng, J. L.; Mu, W.; Zhou, J. F.; Zhu, L. Advances in universal CAR-T cell therapy. Front. Immunol. 2021, 12, 744823.
Ramos, C. A.; Dotti, G. Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy. Exp. Opin. Biol. Ther. 2011, 11, 855–873.
Zhang, C.; Liu, J.; Zhong, J. F.; Zhang, X. Engineering CAR-T cells. Biomark. Res. 2017, 5, 22.
Labanieh, L.; Majzner, R. G.; Mackall, C. L. Programming CAR-T cells to kill cancer. Nat. Biomed. Eng. 2018, 2, 377–391.
Sadelain, M.; Brentjens, R.; Rivière, I. The promise and potential pitfalls of chimeric antigen receptors. Curr. Opin. Immunol. 2009, 21, 215–223.
Roselli, E.; Faramand, R.; Davila, M. L. Insight into next-generation CAR therapeutics: Designing CAR T cells to improve clinical outcomes. J. Clin. Invest. 2021, 131, e142030.
Young, R. M.; Engel, N. W.; Uslu, U.; Wellhausen, N.; June, C. H. Next-generation CAR T-cell therapies. Cancer Discov. 2022, 12, 1625–1633.
Hirsh, V. Next-generation covalent irreversible kinase inhibitors in NSCLC: Focus on afatinib. BioDrugs 2015, 29, 167–183.
Andrea, A. E.; Chiron, A.; Mallah, S.; Bessoles, S.; Sarrabayrouse, G.; Hacein-Bey-Abina, S. Advances in CAR-T cell genetic engineering strategies to overcome hurdles in solid tumors treatment. Front. Immunol. 2022, 13, 830292.
Zhang, X. M.; Zhu, L. L.; Zhang, H.; Chen, S. S.; Xiao, Y. CAR-T cell therapy in hematological malignancies: Current opportunities and challenges. Front. Immunol. 2022, 13, 927153.
Billingsley, M. M.; Hamilton, A. G.; Mai, D.; Patel, S. K.; Swingle, K. L.; Sheppard, N. C.; June, C. H.; Mitchell, M. J. Orthogonal design of experiments for optimization of lipid nanoparticles for mRNA engineering of CAR T cells. Nano Lett. 2022, 22, 533–542.
Ma, L. Y.; Dichwalkar, T.; Chang, J. Y. H.; Cossette, B.; Garafola, D.; Zhang, A. Q.; Fichter, M.; Wang, C. S.; Liang, S.; Silva, M. et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science 2019, 365, 162–168.
Zhang, Z. Z.; Wang, T.; Wang, X. F.; Zhang, Y. Q.; Song, S. X.; Ma, C. Q. Improving the ability of CAR-T cells to hit solid tumors: Challenges and strategies. Pharmacol. Res. 2022, 175, 106036.
Majzner, R. G.; Mackall, C. L. Tumor antigen escape from CAR T-cell therapy. Cancer Discov. 2018, 8, 1219–1226.
Chen, Z.; Pan, H.; Luo, Y. M.; Yin, T.; Zhang, B. Z.; Liao, J. H.; Wang, M. M.; Tang, X. F.; Huang, G. J.; Deng, G. J. et al. Nanoengineered CAR-T biohybrids for solid tumor immunotherapy with microenvironment photothermal-remodeling strategy. Small 2021, 17, 2007494.
Billingsley, M. M.; Singh, N.; Ravikumar, P.; Zhang, R.; June, C. H.; Mitchell, M. J. Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett. 2020, 20, 1578–1589.
Luo, Y. M.; Chen, Z.; Sun, M. J.; Li, B. H.; Pan, F.; Ma, A. Q.; Liao, J. H.; Yin, T.; Tang, X. F.; Huang, G. J. et al. IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy. Biomaterials 2022, 281, 121341.
DiTommaso, T.; Cole, J. M.; Cassereau, L.; Buggé, J. A.; Hanson, J. L. S.; Bridgen, D. T.; Stokes, B. D.; Loughhead, S. M.; Beutel, B. A.; Gilbert, J. B. et al. Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo. Proc. Natl. Acad. Sci. USA 2018, 115, E10907–E10914.
Hajj, K. A.; Whitehead, K. A. Tools for translation: Non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2017, 2, 17056.
Bai, X. W.; Zhou, Y. M.; Yokota, Y.; Matsumoto, Y.; Zhai, B.; Maarouf, N.; Hayashi, H.; Carlson, R.; Zhang, S. H.; Sousa, A. et al. Adaptive antitumor immune response stimulated by bio-nanoparticle based vaccine and checkpoint blockade. J. Exp. Clin. Cancer Res. 2022, 41, 132.
Nakahara, Y.; Kouro, T.; Igarashi, Y.; Kawahara, M.; Sasada, T. Prospects for a personalized peptide vaccine against lung cancer. Exp. Rev. Vacc. 2019, 18, 703–709.
Robbins, P. F.; Lu, Y. C.; El-Gamil, M.; Li, Y. F.; Gross, C.; Gartner, J.; Lin, J. C.; Teer, J. K.; Cliften, P.; Tycksen, E. et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat. Med. 2013, 19, 747–752.
Gubin, M. M.; Zhang, X. L.; Schuster, H.; Caron, E.; Ward, J. P.; Noguchi, T.; Ivanova, Y.; Hundal, J.; Arthur, C. D.; Krebber, W. J. et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014, 515, 577–581.
Chu, Y. H.; Liu, Q.; Wei, J.; Liu, B. R. Personalized cancer neoantigen vaccines come of age. Theranostics 2018, 8, 4238–4246.
Finn, O. J. Cancer vaccines: Between the idea and the reality. Nat. Rev. Immunol. 2003, 3, 630–641.
Vermaelen, K. Vaccine strategies to improve anti-cancer cellular immune responses. Front. Immunol. 2019, 10, 8.
Ding, Z. Y.; Li, Q.; Zhang, R.; Xie, L.; Shu, Y.; Gao, S.; Wang, P. P.; Su, X. Q.; Qin, Y.; Wang, Y. L. et al. Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer. Signal Transduct. Target. Ther. 2021, 6, 26.
Wen, R.; Umeano, A. C.; Kou, Y.; Xu, J.; Farooqi, A. A. Nanoparticle systems for cancer vaccine. Nanomedicine (Lond.) 2019, 14, 627–648.
Wen, R.; Banik, B.; Pathak, R. K.; Kumar, A.; Kolishetti, N.; Dhar, S. Nanotechnology inspired tools for mitochondrial dysfunction related diseases. Adv. Drug Deliv. Rev. 2016, 99, 52–69.
Liu, Q.; Fan, T. J.; Zheng, Y. Y.; Yang, S. L.; Yu, Z. Q.; Duo, Y.; Zhang, Y. H.; Adah, D.; Shi, L. L.; Sun, Z. et al. Immunogenic exosome-encapsulated black phosphorus nanoparticles as an effective anticancer photo-nanovaccine. Nanoscale 2020, 12, 19939–19952.
Xu, Z. H.; Ramishetti, S.; Tseng, Y. C.; Guo, S. T.; Wang, Y. H.; Huang, L. Multifunctional nanoparticles Co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis. J. Control. Release 2013, 172, 259–265.
Li, J.; Li, J. J.; Peng, Y. W.; Du, Y. T.; Yang, Z. Z.; Qi, X. R. Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies. J. Control. Release 2023, 353, 423–433.
Liu, Z. Q.; Shi, M. X.; Ren, Y. Q.; Xu, H.; Weng, S. Y.; Ning, W. J.; Ge, X. Y.; Liu, L.; Guo, C. G.; Duo, M. et al. Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy. Mol. Cancer 2023, 22, 35.
Lacey, S. F.; Fraietta, J. A. First trial of CRISPR-edited t cells in lung cancer. Trends Mol. Med. 2020, 26, 713–715.
Lu, Y.; Xue, J. X.; Deng, T.; Zhou, X. J.; Yu, K.; Deng, L.; Huang, M. J.; Yi, X.; Liang, M. Z.; Wang, Y. et al. Safety and feasibility of CRISPR-edited t cells in patients with refractory non-small-cell lung cancer. Nat. Med. 2020, 26, 732–740.
Duan, L.; Ouyang, K.; Xu, X.; Xu, L. M.; Wen, C. N.; Zhou, X. Y.; Qin, Z.; Xu, Z. Y.; Sun, W.; Liang, Y. J. Nanoparticle delivery of CRISPR/Cas9 for genome editing. Front. Genet. 2021, 12, 673286.
Lakshmanan, V. K.; Jindal, S.; Packirisamy, G.; Ojha, S.; Lian, S.; Kaushik, A.; Alzarooni, A. I. M. A.; Metwally, Y. A. F.; Thyagarajan, S. P.; Do Jung, Y. et al. Nanomedicine-based cancer immunotherapy: Recent trends and future perspectives. Cancer Gene Ther. 2021, 28, 911–923.
Liang, Y. J.; Xu, X.; Xu, L. M.; Prasadam, I.; Duan, L.; Xiao, Y.; Xia, J. Non-surgical osteoarthritis therapy, intra-articular drug delivery towards clinical applications. J. Drug Target. 2021, 29, 609–616.
Sreedurgalakshmi, K.; Srikar, R.; Rajkumari, R. CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries. Cancer Gene Ther. 2021, 28, 566–580.
Zhang, X. F.; Li, B.; Luo, X.; Zhao, W. Y.; Jiang, J.; Zhang, C. X.; Gao, M.; Chen, X. F.; Dong, Y. Z. Biodegradable amino-ester nanomaterials for Cas9 mRNA delivery in vitro and in vivo. ACS Appl. Mater. Interfaces 2017, 9, 25481–25487.
Usman, W. M.; Pham, T. C.; Kwok, Y. Y.; Vu, L. T.; Ma, V.; Peng, B. Y.; Chan, Y. S.; Wei, L. K.; Chin, S. M.; Azad, A. et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat. Commun. 2018, 9, 2359.
Zhu, X. J.; Yu, Z. J.; Feng, L. B.; Deng, L.; Fang, Z. B.; Liu, Z. L.; Li, Y.; Wu, X. R.; Qin, L. Y.; Guo, R. et al. Chitosan-based nanoparticle Co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer. Carbohydr. Polym. 2021, 268, 118237.
Yuba, E.; Tajima, N.; Yoshizaki, Y.; Harada, A.; Hayashi, H.; Kono, K. Dextran derivative-based PH-sensitive liposomes for cancer immunotherapy. Biomaterials 2014, 35, 3091–3101.
Guo, L. R.; Yan, D. D.; Yang, D. F.; Li, Y. J.; Wang, X. D.; Zalewski, O.; Yan, B. F.; Lu, W. Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles. ACS Nano 2014, 8, 5670–5681.
Tang, L.; Zheng, Y. R.; Melo, M. B.; Mabardi, L.; Castaño, A. P.; Xie, Y. Q.; Li, N.; Kudchodkar, S. B.; Wong, H. C.; Jeng, E. K. et al. Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery. Nat. Biotechnol. 2018, 36, 707–716.
Met, Ö.; Jensen, K. M.; Chamberlain, C. A.; Donia, M.; Svane, I. M. Principles of adoptive T cell therapy in cancer. Semin. Immunopathol. 2019, 41, 49–58.
El Achi, H.; Khoury, J. D.; Loghavi, S. Liquid biopsy by next-generation sequencing: A multimodality test for management of cancer. Curr. Hematol. Malig. Rep. 2019, 14, 358–367.
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