In situ vaccination with nanoparticles for cancer immunotherapy: understanding the immunology

References

• Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. Am J Med Sci. 1893;10:487–511.
   Google Scholar
• Coley WB. A report of recent cases of inoperable sarcoma successfully treated with mixed toxins of erysipelas and Bacillus prodigiousus. Surgery, Gynecol Obstet. 1911;13:174.
   Google Scholar
• Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723.
   PubMed Web of Science ®Google Scholar
• Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526.
   PubMed Web of Science ®Google Scholar
• Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol. 2018;8:86.
   PubMed Web of Science ®Google Scholar
• Jessy T. Immunity over inability: the spontaneous regression of cancer. J Nat Sci Biol Med. 2011;2(1):43–49.
   PubMedGoogle Scholar
• Chang S, Kohrt H, Maecker HT. Monitoring the immune competence of cancer patients to predict outcome. Cancer Immunol Immunother. 2014;63(7):713–719.
   PubMed Web of Science ®Google Scholar
• Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801.
   PubMed Web of Science ®Google Scholar
• Mushegian A, Medzhitov R. Evolutionary perspective on innate immune recognition. J Cell Biol. 2001;155(5):705–710.
   PubMed Web of Science ®Google Scholar
• Greenwood B. The contribution of vaccination to global health: past, present and future. Philos Trans R Soc Lond, B, Biol Sci. 2014;369(1645):20130433
   PubMed Web of Science ®Google Scholar
• Doherty M, Buchy P, Standaert B, et al. Vaccine impact: benefits for human health. Vaccine. 2016;34(52):6707–6714.
   PubMed Web of Science ®Google Scholar
• Bloom DE, Canning D, Shenoy ES. The effect of vaccination on children’s physical and cognitivedevelopment in the Philippines. Appl Econ. 2011;44(21):2777–2783.
   Web of Science ®Google Scholar
• Arias-Pulido H, Cimino-Mathews A, Chaher N, et al. The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. Breast Cancer Res Treat. 2018;171(2):273–282.
   PubMed Web of Science ®Google Scholar
• Sarvaria A, Madrigal JA, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol. 2017;14(8):662–674.
   PubMed Web of Science ®Google Scholar
• Burnet FM. Immunological recognition of self. Science. 1961;133(3449):307–311.
   PubMed Web of Science ®Google Scholar
• Houghton AN, Gold JS, Blachere NE. Immunity against cancer: lessons learned from melanoma. Curr Opin Immunol. 2001;13(2):134–140.
   PubMed Web of Science ®Google Scholar
• Ilyas S, Yang JC. Landscape of tumor antigens in T cell immunotherapy. J Immunol. 2015;195(11):5117–5122.
   PubMed Web of Science ®Google Scholar
• Klein G. Tumor antigens. Annu Rev Microbiol. 1966;20:223–252.
   PubMed Web of Science ®Google Scholar
• Klein G, Klein E. Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution. Proc Natl Acad Sci USA. 1977;74(5):2121–2125.
   PubMed Web of Science ®Google Scholar
• Lamon EW. The immune response to virally determined tumor associated antigens. Biochim Biophys Acta. 1974;355(2):149–176.
   PubMed Web of Science ®Google Scholar
• Bonaventura P, Shekarian T, Alcazer V, et al. Cold tumors: a therapeutic challenge for immunotherapy. Front Immunol. 2019;10:168.
   PubMed Web of Science ®Google Scholar
• Maleki Vareki S. High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors. J Immunother Cancer. 2018;6(1):157.
   PubMed Web of Science ®Google Scholar
• Byrne KT, Turk MJ. New perspectives on the role of vitiligo in immune responses to melanoma. Oncotarget. 2011;2(9):684–694.
   PubMed Web of Science ®Google Scholar
• Jiang T, Shi T, Zhang H, et al. Tumor neoantigens: from basic research to clinical applications. J Hematol Oncol. 2019;12(1):93.
   PubMed Web of Science ®Google Scholar
• Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.
   PubMed Web of Science ®Google Scholar
• Peng M, Mo Y, Wang Y, et al. Neoantigen vaccine: an emerging tumor immunotherapy. Mol Cancer. 2019;18(1):128.
   PubMed Web of Science ®Google Scholar
• Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–421.
   PubMed Web of Science ®Google Scholar
• Neefjes J, Jongsma M, Paul P, et al. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11(12):823–836.
   PubMed Web of Science ®Google Scholar
• Ward JP, Gubin MM, Schreiber RD. The Role of Neoantigens in Naturally Occurring and Therapeutically Induced Immune Responses to Cancer. Adv Immunol. 2016;130:25–74.
   PubMed Web of Science ®Google Scholar
• Blum JS, Wearsch PA, Cresswell P. Pathways of antigen processing. Annu Rev Immunol. 2013;31:443–473.
   PubMed Web of Science ®Google Scholar
• Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to pd-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–128.
   PubMed Web of Science ®Google Scholar
• Sharabi A, Kim SS, Kato S, et al. Exceptional response to nivolumab and stereotactic body radiation therapy (sbrt) in neuroendocrine cervical carcinoma with high tumor mutational burden: management considerations from the center for personalized cancer therapy at uc san diego moores cancer center. Oncologist. 2017;22(6):631–637.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–360.
   PubMed Web of Science ®Google Scholar
• Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017;168(4):707–723.
   PubMed Web of Science ®Google Scholar
• Chanmee T, Ontong P, Konno K, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers. 2014;6(3):1670–1690.
   PubMed Web of Science ®Google Scholar
• Kim J, Bae JS. Tumor-associated macrophages and neutrophils in tumor microenvironment. Mediators Inflamm. 2016;2016:6058147.
   PubMed Web of Science ®Google Scholar
• Kerkar SP, Restifo NP. Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 2012;72(13):3125–3130.
   PubMed Web of Science ®Google Scholar
• Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res. 2012;72(9):2162–2171.
   PubMed Web of Science ®Google Scholar
• Janikashvili N, Bonnotte B, Katsanis E, et al. The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance. Clin Dev Immunol. 2011;2011:430394.
   PubMed Web of Science ®Google Scholar
• Rutella S, Danese S, Leone G. Tolerogenic dendritic cells: cytokine modulation comes of age. Blood. 2006;108(5):1435–1440.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–174.
   PubMed Web of Science ®Google Scholar
• Ostrand-Rosenberg S, Fenselau C. Myeloid-derived suppressor cells: immune-suppressive cells that impair antitumor immunity and are sculpted by their environment. J Immunol. 2018;200(2):422–431.
   PubMed Web of Science ®Google Scholar
• Liu Y, Cao X. Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med. 2016;94(5):509–522.
   PubMed Web of Science ®Google Scholar
• Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541–550.
   PubMed Web of Science ®Google Scholar
• Young A, Quandt Z, Bluestone JA. The balancing act between cancer immunity and autoimmunity in response to immunotherapy. Cancer Immunol Res. 2018;6(12):1445–1452.
   PubMed Web of Science ®Google Scholar
• Martins F, Sofiya L, Sykiotis GP, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563–580.
   PubMed Web of Science ®Google Scholar
• Li B, Chan HL, Chen P. Immune checkpoint inhibitors: basics and challenges. Curr Med Chem. 2019;26(17):3009–3025.
   PubMed Web of Science ®Google Scholar
• Zappasodi R, Merghoub T, Wolchok JD. Emerging concepts for immune checkpoint blockade-based combination therapies. Cancer Cell. 2018;33(4):581–598.
   PubMed Web of Science ®Google Scholar
• Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218.
   PubMed Web of Science ®Google Scholar
• Ishihara D, Pop L, Takeshima T, et al. Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment. Cancer Immunol Immunother. 2017;66(3):281–298.
   PubMed Web of Science ®Google Scholar
• Min Y, Roche KC, Tian S, et al. Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy. Nat Nanotechnol. 2017;12(9):877–882.
   PubMed Web of Science ®Google Scholar
• Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
   PubMed Web of Science ®Google Scholar
• Bouzid R, Peppelenbosch M, Buschow SI. Opportunities for conventional and in situ cancer vaccine strategies and combination with immunotherapy for gastrointestinal cancers. A Review. Cancers. 2020;12(5):1121.
   Web of Science ®Google Scholar
• Sheen MR, Fiering S. In situ vaccination: harvesting low hanging fruit on the cancer immunotherapy tree. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2019;11(1):e1524.
   PubMed Web of Science ®Google Scholar
• JAMA Network. The failure of the erysipelas toxins. JAMA. 1894;24:919.
   Google Scholar
• Goto T. Radiation as an in situ auto-vaccination: current perspectives and challenges. Vaccines. 2019;7(3):100.
   Web of Science ®Google Scholar
• Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Oncol Biol Phys. 2012;84(4):879–880.
   PubMed Web of Science ®Google Scholar
• Hoopes PJ, Moodie KL, Petryk AA, et al. 2017. Hypo-fractionated radiation, magnetic nanoparticle hyperthermia and a viral immunotherapy treatment of spontaneous canine cancer. Paper presented at the Proceedings of SPIE–the International Society for Optical Engineering, 2017 February 22, San Fransisco, CA.
   Google Scholar
• Hoffman HA, Chakrabarti L, Dumont MF, et al. Prussian blue nanoparticles for laser-induced photothermal therapy of tumors. RSC Adv. 2014;4(56):29729–29734.
   Web of Science ®Google Scholar
• Burga RA, Patel S, Bollard CM, et al. Conjugating Prussian blue nanoparticles onto antigen-specific T cells as a combined nanoimmunotherapy. Nanomedicine. 2016;11(14):1759–1767.
   PubMed Web of Science ®Google Scholar
• Cai Z, Xin F, Wei Z, et al. Photodynamic therapy combined with antihypoxic signaling and CpG adjuvant as an in situ tumor vaccine based on metal-organic framework nanoparticles to boost cancer immunotherapy. Adv Healthc Mater. 2020;9(1):e1900996.
   PubMed Web of Science ®Google Scholar
• Toraya-Brown S, Fiering S. Local tumour hyperthermia as immunotherapy for metastatic cancer. Int J Hyperthermia. 2014;30(8):531–539.
   PubMed Web of Science ®Google Scholar
• van den Bijgaart RJ, Eikelenboom DC, Hoogenboom M, et al. Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies. Cancer Immunol Immunother. 2017;66(2):247–258.
   PubMed Web of Science ®Google Scholar
• Mole R H. Whole body irradiation; radiobiology or medicine? Br J Radiol. 1953;26(305):234–241.
   PubMed Web of Science ®Google Scholar
• Nobler MP. The abscopal effect in malignant lymphoma and its relationship to lymphocyte circulation. Radiology. 1969;93(2):410–412.
   PubMed Web of Science ®Google Scholar
• Lome LG, Navani S, Aral IM. Spontaneous regression of pulmonary metastases from transitional cell carcinoma of the bladder. Cancer. 1970;26(2):415–418.
   PubMed Web of Science ®Google Scholar
• Kingsley DP. An interesting case of possible abscopal effect in malignant melanoma. Br J Radiol. 1975;48(574):863–866.
   PubMed Web of Science ®Google Scholar
• Demaria S, Ng B, Devitt ML, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004;58(3):862–870.
   PubMed Web of Science ®Google Scholar
• Brix N, Tiefenthaller A, Anders H, et al. Abscopal, immunological effects of radiotherapy: narrowing the gap between clinical and preclinical experiences. Immunol Rev. 2017;280(1):249–279.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Buque A, Kepp O, et al. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97–111.
   PubMed Web of Science ®Google Scholar
• Kroemer G, Galluzzi L, Kepp O, et al. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.
   PubMed Web of Science ®Google Scholar
• Tesniere A, Panaretakis T, Kepp O, et al. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ. 2008;15(1):3–12.
   PubMed Web of Science ®Google Scholar
• Lin FC, Hsu CH, Lin YY. Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling. Int J Nanomedicine. 2018;13:3529–3539.
   PubMed Web of Science ®Google Scholar
• Jego G, Hazoumé A, Seigneuric R, et al. Targeting heat shock proteins in cancer. Cancer Lett. 2013;332(2):275–285.
   PubMed Web of Science ®Google Scholar
• Zhou J, Wang G, Chen Y, et al. Immunogenic cell death in cancer therapy: present and emerging inducers. J Cell Mol Med. 2019;23(8):4854–4865.
   PubMed Web of Science ®Google Scholar
• Wennerberg E, Lhuillier C, Vanpouille-Box C, et al. Barriers to radiation-induced in situ tumor vaccination. Front Immunol. 2017;8:229.
   PubMed Web of Science ®Google Scholar
• Sethuraman SN, Singh MP, Patil G, et al. Novel calreticulin-nanoparticle in combination with focused ultrasound induces immunogenic cell death in melanoma to enhance antitumor immunity. Theranostics. 2020;10(8):3397–3412.
   PubMed Web of Science ®Google Scholar
• Sagiv-Barfi I, Czerwinski DK, Levy S, et al. Eradication of spontaneous malignancy by local immunotherapy. Sci Transl Med. 2018;10(426):eaan4488.
   PubMed Web of Science ®Google Scholar
• Kreiter S, Vormehr M, van de Roemer N, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520(7549):692–696.
   PubMed Web of Science ®Google Scholar
• Hammerich L, Marron TU, Upadhyay R, et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019;25(5):814–824.
   PubMed Web of Science ®Google Scholar
• Hugander A, Hafström L, Jönsson PE, et al. Local hyperthermia in treatment of experimental liver tumors. Cancer. 1984;53(8):1686–1691.
   PubMed Web of Science ®Google Scholar
• Ostapenko VV, Tanaka H, Miyano M, et al. Immune-related effects of local hyperthermia in patients with primary liver cancer. Hepato-gastroenterology. 2005;52(65):1502–1506.
   PubMedGoogle Scholar
• McDermott S, Gervais DA. Radiofrequency ablation of liver tumors. Semin Intervent Radiol. 2013;30(1):49–55.
   PubMed Web of Science ®Google Scholar
• Toraya-Brown S, Sheen MR, Zhang P, et al. Local hyperthermia treatment of tumors induces CD8(+) T cell-mediated resistance against distal and secondary tumors. Nanomedicine. 2014;10(6):1273–1285.
   PubMed Web of Science ®Google Scholar
• Chen H, Kuo MT. Improving radiotherapy in cancer treatment: promises and challenges. Oncotarget. 2017;8(37):62742–62758.
   PubMedGoogle Scholar
• Demicheli R, Retsky MW, Hrushesky WJ, et al. The effects of surgery on tumor growth: a century of investigations. Ann Oncol. 2008;19(11):1821–1828.
   PubMed Web of Science ®Google Scholar
• Richman SP, Gutterman JU, Hersh EM. Cancer immunotherapy. Can Med Assoc J. 1979;120(3):322–324.
   PubMed Web of Science ®Google Scholar
• Old LJ, Clarke DA, Benacerraf B. Effect of Bacillus Calmette-Guerin infection on transplanted tumours in the mouse. Nature. 1959;184(5):291–292.
   PubMed Web of Science ®Google Scholar
• deKernion JB, Golub SH, Gupta RK, et al. Successful transurethral intralesional BCG therapy of a bladder melanoma. Cancer. 1975;36(5):1662–1667.
   PubMed Web of Science ®Google Scholar
• Lamm DL, Thor DE, Harris SC, et al. Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. J Urol. 1980;124(1):38–40.
   PubMed Web of Science ®Google Scholar
• Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–183.
   PubMed Web of Science ®Google Scholar
• Herr HW, Morales A. History of Bacillus Calmette-Guerin and bladder cancer: an immunotherapy success story. J Urol. 2008;179(1):53–56.
   PubMed Web of Science ®Google Scholar
• Rehman H, Silk AW, Kane MP, et al. Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy. J Immunother Cancer. 2016;4:53.
   PubMed Web of Science ®Google Scholar
• Hawkins LK, Lemoine NR, Kirn D. Oncolytic biotherapy: a novel therapeutic platform. The Lancet Oncol. 2002;3(1):17–26.
   PubMed Web of Science ®Google Scholar
• Thompson JF, Agarwala SS, Smithers BM, et al. Phase 2 study of intralesional PV-10 in refractory metastatic melanoma. Ann Surg Oncol. 2015;22(7):2135–2142.
   PubMed Web of Science ®Google Scholar
• Swift L, Zhang C, Trippett T, et al. Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma. Onco Targets Ther. 2019;12:1293–1307.
   PubMed Web of Science ®Google Scholar
• Liu H, Innamarato PP, Kodumudi K, et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget. 2016;7(25):37893–37905.
   PubMedGoogle Scholar
• Liu H, Weber A, Morse J, et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PloS One. 2018;13(4):e0196033.
   PubMed Web of Science ®Google Scholar
• Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46(12):6387–6392.
   PubMed Web of Science ®Google Scholar
• Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71–79.
   PubMed Web of Science ®Google Scholar
• Iyer AK, Khaled G, Fang J, et al. Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today. 2006;11(17–18):812–818.
   PubMed Web of Science ®Google Scholar
• Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul. 2001;41:189–207.
   PubMedGoogle Scholar
• Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19(14):3312–3322.
   PubMed Web of Science ®Google Scholar
• Nichols JW, Bae YH. EPR: evidence and fallacy. J Control Release. 2014;190:451–464.
   PubMed Web of Science ®Google Scholar
• Danhier F. To exploit the tumor microenvironment: since the EPR effect fails in the clinic, what is the future of nanomedicine? J Control Release. 2016;244(A):108–121.
   PubMed Web of Science ®Google Scholar
• Rawat M, Singh D, Saraf S, et al. Nanocarriers: promising vehicle for bioactive drugs. Biol Pharm Bull. 2006;29(9):1790–1798.
   PubMed Web of Science ®Google Scholar
• Holback H, Yeo Y. Intratumoral drug delivery with nanoparticulate carriers. Pharm Res. 2011;28(8):1819–1830.
   PubMed Web of Science ®Google Scholar
• Sau S, Agarwalla P, Mukherjee S, et al. Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle. Nanoscale. 2014;6(12):6745–6754.
   PubMed Web of Science ®Google Scholar
• Conniot J, Silva JM, Fernandes JG, et al. Cancer immunotherapy: nanodelivery approaches for immune cell targeting and tracking. Front Chem. 2014;2:105.
   PubMed Web of Science ®Google Scholar
• Aghebati-Maleki A, Dolati S, Ahmadi M, et al. Nanoparticles and cancer therapy: perspectives for application of nanoparticles in the treatment of cancers. J Cell Physiol. 2020;235(3):1962–1972.
   PubMed Web of Science ®Google Scholar
• Sau S, Alsaab HO, Bhise K, et al. Multifunctional nanoparticles for cancer immunotherapy: a groundbreaking approach for reprogramming malfunctioned tumor environment. J Control Release. 2018;274:24–34.
   PubMed Web of Science ®Google Scholar
• Lee IH, Kwon HK, An S, et al. Imageable antigen-presenting gold nanoparticle vaccines for effective cancer immunotherapy in vivo. Angew Chem Int Ed Engl. 2012;51(35):8800–8805.
   PubMed Web of Science ®Google Scholar
• Toraya-Brown S, Sheen MR, Baird JR, et al. Phagocytes mediate targeting of iron oxide nanoparticles to tumors for cancer therapy. Integr Biol. 2013;5(1):159–171.
   Google Scholar
• Mukherjee S, Ray S, Thakur R. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71(4):349–358.
   PubMed Web of Science ®Google Scholar
• Lizotte PH, Wen AM, Sheen MR, et al. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nat Nanotechnol. 2016;11(3):295–303.
   PubMed Web of Science ®Google Scholar
• Liu D, Poon C, Lu K, et al. Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy. Nat Commun. 2014;5:4182.
   PubMed Web of Science ®Google Scholar
• Vesely MD, Kershaw MH, Schreiber RD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–271.
   PubMed Web of Science ®Google Scholar
• Alexis F, Pridgen E, Molnar LK, et al. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5(4):505–515.
   PubMed Web of Science ®Google Scholar
• Bertrand N, Wu J, Xu X, et al. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2–25.
   PubMed Web of Science ®Google Scholar
• Fay F, Scott CJ. Antibody-targeted nanoparticles for cancer therapy. Immunotherapy. 2011;3(3):381–394.
   PubMed Web of Science ®Google Scholar
• Carter T, Mulholland P, Chester K. Antibody-targeted nanoparticles for cancer treatment. Immunotherapy. 2016;8(8):941–958.
   PubMed Web of Science ®Google Scholar
• Rosenblum D, Joshi N, Tao W, et al. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun. 2018;9(1):1410.
   PubMed Web of Science ®Google Scholar
• Gustafson HH, Holt-Casper D, Grainger DW, et al. Nanoparticle uptake: the phagocyte problem. Nano Today. 2015;10(4):487–510.
   PubMed Web of Science ®Google Scholar
• Janßen HC, Angrisani N, Kalies S, et al. Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics. J Nanobiotechnology. 2020;18(1):14.
   PubMed Web of Science ®Google Scholar
• Lança T, Silva-Santos B. The split nature of tumor-infiltrating leukocytes: implications for cancer surveillance and immunotherapy. Oncoimmunology. 2012;1(5):717–725.
   PubMed Web of Science ®Google Scholar
• Mittal D, Gubin MM, Schreiber RD, et al. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol. 2014;27:16–25.
   PubMed Web of Science ®Google Scholar
• Sheen MR, Lizotte PH, Toraya-Brown S, et al. Stimulating antitumor immunity with nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014;6(5):496–505.
   PubMed Web of Science ®Google Scholar
• Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol. 2013;4:114.
   PubMed Web of Science ®Google Scholar
• Lee KL, Murray AA, Le DHT, et al. Combination of plant virus nanoparticle-based in situ vaccination with chemotherapy potentiates antitumor response. Nano Lett. 2017;17(7):4019–4028.
   PubMed Web of Science ®Google Scholar
• Lee JM, Lee MH, Garon E, et al. Phase I trial of intratumoral injection of CCL21 gene-modified dendritic cells in lung cancer elicits tumor-specific immune responses and CD8+ T-cell infiltration. Clin Cancer Res. 2017;23(16):4556–4568.
   PubMed Web of Science ®Google Scholar
• Le DH, Lee KL, Shukla S, et al. Potato virus X, a filamentous plant viral nanoparticle for doxorubicin delivery in cancer therapy. Nanoscale. 2017;9(6):2348–2357.
   PubMed Web of Science ®Google Scholar
• Amarante-Mendes GP, Adjemian S, Branco LM, et al. Pattern recognition receptors and the host cell death molecular machinery. Front Immunol. 2018;9:2379.
   PubMed Web of Science ®Google Scholar
• Rosenfeld MR, Chamberlain MC, Grossman SA, et al. A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro-Oncology. 2010;12(10):1071–1077.
   PubMed Web of Science ®Google Scholar
• Hammerich L, Binder A, Brody JD. In situ vaccination: cancer immunotherapy both personalized and off-the-shelf. Mol Oncol. 2015;9(10):1966–1981.
   PubMed Web of Science ®Google Scholar
• Salazar AM, Erlich RB, Mark A, et al. Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial. Cancer Immunol Res. 2014;2(8):720–724.
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan V, Helmink BA, Spencer CN, et al. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33(4):570–580.
   PubMed Web of Science ®Google Scholar
• Fessler J, Matson V, Gajewski TF. Exploring the emerging role of the microbiome in cancer immunotherapy. J Immunother Cancer. 2019;7(1):108.
   PubMed Web of Science ®Google Scholar
• Roger A, Finet A, Boru B, et al. Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients. Oncoimmunology. 2018;7(7):e1442166.
   PubMed Web of Science ®Google Scholar
• Hammerich L, Davis TA, Keler T, et al. Combining in situ vaccination with immune checkpoint blockade induces long-term regression of lymphoma tumors. Blood. 2016;128(22):465–465.
   PubMed Web of Science ®Google Scholar
• Khalil DN, Suek N, Campesato LF, et al. In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors. J Clin Invest. 2019;129(8):3435–3447.
   PubMed Web of Science ®Google Scholar
• Atkins MB, Robertson MJ, Gordon M, et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res. 1997;3(3):409–417.
   PubMed Web of Science ®Google Scholar
• Leonard JP, Sherman ML, Fisher GL, et al. Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production. Blood. 1997;90(7):2541–2548.
   PubMed Web of Science ®Google Scholar
• Fiszer-Maliszewska L, Den Otter W, Madej JA, et al. Therapeutic potential of biological response modifiers against transplantable mouse tumors of spontaneous origin. II. Local interleukin 2 treatment of tumors of different immunogenic strength. Arch Immunol Ther Exp. 1998;46(5):293–300.
   PubMedGoogle Scholar
• Radny P, Caroli UM, Bauer J, et al. Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br J Cancer. 2003;89(9):1620–1626.
   PubMed Web of Science ®Google Scholar
• Weide B, Derhovanessian E, Pflugfelder A, et al. High response rate after intratumoral treatment with interleukin-2: results from a phase 2 study in 51 patients with metastasized melanoma. Cancer. 2010;116(17):4139–4146.
   PubMed Web of Science ®Google Scholar
• Spitzer MH, Carmi Y, Reticker-Flynn NE, et al. Systemic immunity is required for effective cancer immunotherapy. Cell. 2017;168(3):487–502.
   PubMed Web of Science ®Google Scholar