肿瘤治疗中细胞因子递送策略的研究进展
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摘要
细胞因子多数是由机体免疫细胞和某些非免疫细胞产生的,对细胞的生长、增殖、分化均有调节作用的一类具有生物活性的蛋白质。在肿瘤治疗中,细胞因子作为一种蛋白质药物,具有体内半衰期短、全身毒副作用大等特点,因而选择细胞因子递送策略时需考虑以上因素。文章简要介绍了几种常见的细胞因子,并综述了近年来在肿瘤治疗中细胞因子递送策略的研究进展。
Cytokines, mainly produced by immune cells and some non-immune cells, are a kind of bioactive protein and play an important role in cell growth, proliferation, and differentiation. In tumor therapy, the properties of cytokines such as short half-life and side effects in high dosage, should be considered when selecting suitable delivery strategies. Several common cytokines were simply summarized, and research progress of delivery strategies for cytokines in tumor therapy was reviewed in this article.
Cytokines, mainly produced by immune cells and some non-immune cells, are a kind of bioactive protein and play an important role in cell growth, proliferation, and differentiation. In tumor therapy, the properties of cytokines such as short half-life and side effects in high dosage, should be considered when selecting suitable delivery strategies. Several common cytokines were simply summarized, and research progress of delivery strategies for cytokines in tumor therapy was reviewed in this article.
引文
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[7]Jiang T,Zhou C,Ren S.Role of IL-2 in cancer immunotherapy.Oncoimmunology,2016,5(6):e1163462
[8]Freytag SO,Barton KN,Zhang Y.Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12in preclinical model of prostate cancer.Gene Ther,2013,20(12):1131-1139
[9]Yarchoan R1,Pluda JM,Wyvill KM,et al.Treatment of AIDS-related Kaposi’s sarcoma with interleukin-12:rationale and preliminary evidence of clinical activity.Crit Rev Immunol,2007,27(5):401-414
[10]Stephen MA,Thomas EW,Paul JK,et al.Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma.Blood,2002,99:67-74
[11]Conlon KC,Lugli E,Welles HC,et al.Redistribution,hyperproliferation,activation of natural killer cells and CD8 T cells,and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.J Clin Oncol,2015,33(1):74-82
[12]Bekisz J,Sato Y,Johnson C,et al.Immunomodulatory effects of interferons in malignancies.J Interferon Cytokine Res,2013,33(4):154-161
[13]Negrier S,Perol D,Ravaud A,et al.Randomized study of intravenous versus subcutaneous interleukin-2,and IF-Nalpha in patients with good prognosis metastatic renal cancer.Clin Cancer Res,2008,14(18):5907-5912
[14]Mauldin IS,Wages NA,Stowman AM,et al.Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases.Cancer Immunol Immunother,2016,65(10):1189-1199
[15]Milling L,Zhang Y,Irvine DJ.Delivering safer immunotherapies for cancer.Adv Drug Deliv Rev 2017,114:79-101
[16]Song Q,Yin Y,Shang L,et al.Tumor microenvironment responsive nanogel for the combinatorial antitumor effect of chemotherapy and immunotherapy.Nano Lett,2017,17(10):6366-6375
[17]Lv XZ,Zheng MY,Lin ZQ,et al.Granzyme B-truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC.Oral Dis,2016,22(7):688-696
[18]Ilona R,Evzen K.Granzyme B-induced apoptosis in cancer cells and its regulation.Int J Oncol,2010,37(6):1361-1378
[19]Hemmerle T,Neri D.The dose-dependent tumor targeting of antibody-IFNgamma fusion proteins reveals an unexpected receptor-trapping mechanism in vivo.Cancer Immunol Res,2014,2(6):559-567
[20]Minn AJ,Wherry EJ.Combination cancer therapies with immune checkpoint blockade:convergence on interferon signaling.Cell,2016,165(2):272-275
[21]Secombes CJ,Zou J.Evolution of interferons and interferon receptors.Front Immunol,2017,8:209
[22]Wu X,He C,Wu Y,et al.Nanogel-incorporated physical and chemical hybrid gels for highly effective chemo-protein combination therapy.Adv Funct Mater,2015,25(43):6744-6755
[23]He CL,Tang ZH,Tian HY,et al.Co-delivery of chemotherapeutics and proteins for synergistic therapy.Adv Drug Deliv Rev,2016,98:64-76
[24]Schellekens H,Hennink WE,Brinks V.The immunogenicity of polyethylene glycol:facts and fiction.Pharm Res,2013,30(7):1729-1734
[25]Mitragotri S,Burke PA,Langer R.Overcoming the challenges in administering biopharmaceuticals:formulation and delivery strategies.Nat Rev Drug Discov,2014,13(9):655-672
[26]Hu J,Wang G,Zhao W,et al.Site-specific in situ growth of an interferon-polymer conjugate that outperforms PEGASYS in cancer therapy.Biomaterials,2016,96:84-92
[27]Cobo I,Li M,Sumerlin BS,et al.Smart hybrid materials by conjugation of responsive polymers to biomacromolecules.Nat Mater,2015,14(2):143-159
[28]Yamada Y,Aoyama A,Tocco G,et al.Differential effects of denileukin diftitox IL-2 immunotoxin on NK and regulatory T cells in nonhuman primates.J Immunol,2012,188(12):6063-6070
[29]Jang B,Kwon H,Katila P,et al.Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.Adv Drug Deliv Rev,2016,98:113-133
[30]Dong M,Zhang HB,Kai T,et al.Novel supramolecular hydrogel/micelle composite for co-delivery of anticancer drug and growth factor.Soft Matter,2012,8(13):3665
[31]Ten Hagen TLM,Seynhaeve ALB,Van Tiel ST,et al.Pegylated liposomal tumor necosis factor-αreaults in reduced toxicity and synergistic antitumor activity after systemic administartion in combination with liposomal Doxorubicin(DOXIL?)in soft tissue sarcoma-bearing rats Int J.Cancer,2002,97:115-120
[32]Wang Y,Lin YX,Qiao SL,et al.Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment.Biomaterials,2017,112:153-163
[33]Miki K,Nagaoka K,Harada M,et al.Combination therapy with dendritic cell vaccine and IL-2 encapsulating polymeric micelles enhances intra-tumoral accumulation of antigen-specific CTLs.Int Immunopharmacol,2014,23(2):499-504
[34]Jiang T,Mo R,Bellotti A,et al.Gel-liposome-mediated co-delivery of anticancer membrane-associated proteins and small-molecule drugs for enhanced therapeutic efficacy.Adv Funct Mater,2014,24(16):2295-2304
[35]Pachioni-Vasconcelos Jde A,Lopes AM,Apolinario AC,et al.Nanostructures for protein drug delivery.Biomater Sci,2016,4(2):205-218
[36]Meraz IM,Savage DJ,Segura-Ibarra V,et al.Adjuvant cationic liposomes presenting MPL and IL-12 induce cell death,suppress tumor growth,and alter the cellular phenotype of tumors in a murine model of breast cancer.Mol Pharm,2014,11(10):3484-3491
[37]Zhang Y,Li N,Suh H,et al.Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity.Nat Commun,2018,9(1):6
[38]Lu L,Zou Y,Yang W,et al.Anisamide-decorated pH-sensitive degradable chimaeric polymersomes mediate potent and targeted protein delivery to lung cancer cells.Biomacromolecules,2015,16(6):1726-1735
[39]Li X,Yang W,Zou Y,et al.Efficacious delivery of protein drugs to prostate cancer cells by PSMA-targeted pH-responsive chimaeric polymersomes.J Control Release,2015,220:704-714
[40]Molina M,Asadian-Birjand M,Balach J,et al.Stimuli-responsive nanogel composites and their application in nanomedicine.Chem Soc Rev,2015,44:6161-6186
[41]Shimizu T,Kishida T,Hasegawa U,et al.Nanogel DDSenables sustained release of IL-12 for tumor immunotherapy.Biochem Biophys Res Commun,2008,367(2):330-335
[42]Chen J,Zou Y,Deng C,et al.Multifunctional click hyaluronic acid nanogels for targeted proteindelivery and effective cancer treatment in vivo.Chem Mater,2016,28(23):8792-8799
[43]Vermonden T,Censi R,Hennink WE.Hydrogels for protein delivery.Chem Rev,2012,112(5):2853-2888
[44]Seo SH,Han HD,Noh KH,et al.Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8+T cell-mediated anti-tumor immunity.Clin Exp Metastasis,2009,26(3):179-187
[45]Wu X,Wu Y,Ye H,et al.Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy.J Control Release,2017,255:81-93
[46]Buwalda SJ,Boere KW,Dijkstra PJ,et al.Hydrogels in a historical perspective:from simple networks to smart materials.J Control Release,2014,190:254-273
[47]Kim CS,Mout R,Zhao Y,et al.Co-delivery of protein and small molecule therapeutics using nanoparticle-stabilized nanocapsules.Bioconjug Chem,2015,26(5):950-954
[48]Tahara Y,Akiyoshi K.Current advances in self-assembled nanogel delivery systems for immunotherapy.Adv Drug Deliv Rev,2015,95:65-76
[49]Cook AM,Lesterhuis WJ,Nowak AK,et al.Chemotherapy and immunotherapy:mapping the road ahead.Curr Opin Immunol,2016,39:23-29
[2]Yu M,Wu J,Shi J,et al.Nanotechnology for protein delivery:overview and perspectives.J Control Release,2016,240:24-37
[3]Gu Z,Biswas A,Zhao M,et al.Tailoring nanocarriers for intracellular protein delivery.Chem Soc Rev,2011,40(7):3638-3655
[4]Becher B,Spath S,Goverman J.Cytokine networks in neuroinflammation.Nat Rev Immunol,2017,17(1):49-59
[5]Kursunel MA,Esendagli G.The untold story of IFN-gamma in cancer biology.Cytokine Growth Factor Rev,2016,31:73-81
[6]Klapper JA,Downey SG,Smith FO,et al.High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma:a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006.Cancer,2008,113(2):293-301
[7]Jiang T,Zhou C,Ren S.Role of IL-2 in cancer immunotherapy.Oncoimmunology,2016,5(6):e1163462
[8]Freytag SO,Barton KN,Zhang Y.Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12in preclinical model of prostate cancer.Gene Ther,2013,20(12):1131-1139
[9]Yarchoan R1,Pluda JM,Wyvill KM,et al.Treatment of AIDS-related Kaposi’s sarcoma with interleukin-12:rationale and preliminary evidence of clinical activity.Crit Rev Immunol,2007,27(5):401-414
[10]Stephen MA,Thomas EW,Paul JK,et al.Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma.Blood,2002,99:67-74
[11]Conlon KC,Lugli E,Welles HC,et al.Redistribution,hyperproliferation,activation of natural killer cells and CD8 T cells,and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.J Clin Oncol,2015,33(1):74-82
[12]Bekisz J,Sato Y,Johnson C,et al.Immunomodulatory effects of interferons in malignancies.J Interferon Cytokine Res,2013,33(4):154-161
[13]Negrier S,Perol D,Ravaud A,et al.Randomized study of intravenous versus subcutaneous interleukin-2,and IF-Nalpha in patients with good prognosis metastatic renal cancer.Clin Cancer Res,2008,14(18):5907-5912
[14]Mauldin IS,Wages NA,Stowman AM,et al.Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases.Cancer Immunol Immunother,2016,65(10):1189-1199
[15]Milling L,Zhang Y,Irvine DJ.Delivering safer immunotherapies for cancer.Adv Drug Deliv Rev 2017,114:79-101
[16]Song Q,Yin Y,Shang L,et al.Tumor microenvironment responsive nanogel for the combinatorial antitumor effect of chemotherapy and immunotherapy.Nano Lett,2017,17(10):6366-6375
[17]Lv XZ,Zheng MY,Lin ZQ,et al.Granzyme B-truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC.Oral Dis,2016,22(7):688-696
[18]Ilona R,Evzen K.Granzyme B-induced apoptosis in cancer cells and its regulation.Int J Oncol,2010,37(6):1361-1378
[19]Hemmerle T,Neri D.The dose-dependent tumor targeting of antibody-IFNgamma fusion proteins reveals an unexpected receptor-trapping mechanism in vivo.Cancer Immunol Res,2014,2(6):559-567
[20]Minn AJ,Wherry EJ.Combination cancer therapies with immune checkpoint blockade:convergence on interferon signaling.Cell,2016,165(2):272-275
[21]Secombes CJ,Zou J.Evolution of interferons and interferon receptors.Front Immunol,2017,8:209
[22]Wu X,He C,Wu Y,et al.Nanogel-incorporated physical and chemical hybrid gels for highly effective chemo-protein combination therapy.Adv Funct Mater,2015,25(43):6744-6755
[23]He CL,Tang ZH,Tian HY,et al.Co-delivery of chemotherapeutics and proteins for synergistic therapy.Adv Drug Deliv Rev,2016,98:64-76
[24]Schellekens H,Hennink WE,Brinks V.The immunogenicity of polyethylene glycol:facts and fiction.Pharm Res,2013,30(7):1729-1734
[25]Mitragotri S,Burke PA,Langer R.Overcoming the challenges in administering biopharmaceuticals:formulation and delivery strategies.Nat Rev Drug Discov,2014,13(9):655-672
[26]Hu J,Wang G,Zhao W,et al.Site-specific in situ growth of an interferon-polymer conjugate that outperforms PEGASYS in cancer therapy.Biomaterials,2016,96:84-92
[27]Cobo I,Li M,Sumerlin BS,et al.Smart hybrid materials by conjugation of responsive polymers to biomacromolecules.Nat Mater,2015,14(2):143-159
[28]Yamada Y,Aoyama A,Tocco G,et al.Differential effects of denileukin diftitox IL-2 immunotoxin on NK and regulatory T cells in nonhuman primates.J Immunol,2012,188(12):6063-6070
[29]Jang B,Kwon H,Katila P,et al.Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.Adv Drug Deliv Rev,2016,98:113-133
[30]Dong M,Zhang HB,Kai T,et al.Novel supramolecular hydrogel/micelle composite for co-delivery of anticancer drug and growth factor.Soft Matter,2012,8(13):3665
[31]Ten Hagen TLM,Seynhaeve ALB,Van Tiel ST,et al.Pegylated liposomal tumor necosis factor-αreaults in reduced toxicity and synergistic antitumor activity after systemic administartion in combination with liposomal Doxorubicin(DOXIL?)in soft tissue sarcoma-bearing rats Int J.Cancer,2002,97:115-120
[32]Wang Y,Lin YX,Qiao SL,et al.Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment.Biomaterials,2017,112:153-163
[33]Miki K,Nagaoka K,Harada M,et al.Combination therapy with dendritic cell vaccine and IL-2 encapsulating polymeric micelles enhances intra-tumoral accumulation of antigen-specific CTLs.Int Immunopharmacol,2014,23(2):499-504
[34]Jiang T,Mo R,Bellotti A,et al.Gel-liposome-mediated co-delivery of anticancer membrane-associated proteins and small-molecule drugs for enhanced therapeutic efficacy.Adv Funct Mater,2014,24(16):2295-2304
[35]Pachioni-Vasconcelos Jde A,Lopes AM,Apolinario AC,et al.Nanostructures for protein drug delivery.Biomater Sci,2016,4(2):205-218
[36]Meraz IM,Savage DJ,Segura-Ibarra V,et al.Adjuvant cationic liposomes presenting MPL and IL-12 induce cell death,suppress tumor growth,and alter the cellular phenotype of tumors in a murine model of breast cancer.Mol Pharm,2014,11(10):3484-3491
[37]Zhang Y,Li N,Suh H,et al.Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity.Nat Commun,2018,9(1):6
[38]Lu L,Zou Y,Yang W,et al.Anisamide-decorated pH-sensitive degradable chimaeric polymersomes mediate potent and targeted protein delivery to lung cancer cells.Biomacromolecules,2015,16(6):1726-1735
[39]Li X,Yang W,Zou Y,et al.Efficacious delivery of protein drugs to prostate cancer cells by PSMA-targeted pH-responsive chimaeric polymersomes.J Control Release,2015,220:704-714
[40]Molina M,Asadian-Birjand M,Balach J,et al.Stimuli-responsive nanogel composites and their application in nanomedicine.Chem Soc Rev,2015,44:6161-6186
[41]Shimizu T,Kishida T,Hasegawa U,et al.Nanogel DDSenables sustained release of IL-12 for tumor immunotherapy.Biochem Biophys Res Commun,2008,367(2):330-335
[42]Chen J,Zou Y,Deng C,et al.Multifunctional click hyaluronic acid nanogels for targeted proteindelivery and effective cancer treatment in vivo.Chem Mater,2016,28(23):8792-8799
[43]Vermonden T,Censi R,Hennink WE.Hydrogels for protein delivery.Chem Rev,2012,112(5):2853-2888
[44]Seo SH,Han HD,Noh KH,et al.Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8+T cell-mediated anti-tumor immunity.Clin Exp Metastasis,2009,26(3):179-187
[45]Wu X,Wu Y,Ye H,et al.Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy.J Control Release,2017,255:81-93
[46]Buwalda SJ,Boere KW,Dijkstra PJ,et al.Hydrogels in a historical perspective:from simple networks to smart materials.J Control Release,2014,190:254-273
[47]Kim CS,Mout R,Zhao Y,et al.Co-delivery of protein and small molecule therapeutics using nanoparticle-stabilized nanocapsules.Bioconjug Chem,2015,26(5):950-954
[48]Tahara Y,Akiyoshi K.Current advances in self-assembled nanogel delivery systems for immunotherapy.Adv Drug Deliv Rev,2015,95:65-76
[49]Cook AM,Lesterhuis WJ,Nowak AK,et al.Chemotherapy and immunotherapy:mapping the road ahead.Curr Opin Immunol,2016,39:23-29