肿瘤抗体治疗的现状与发展趋势

徐增辉; 钱其军

肿瘤抗体治疗的现状与发展趋势

中国人民解放军第二军医大学东方肝胆外科医院基因与病毒治疗实验室

基金项目:

国家杰出青年科学基金(30925037)；上海市优秀学科带头人A计划(10XD1406500)；

详细信息

中图分类号: R730.5
计量
- 文章访问数: 4176
- HTML全文浏览量: 23
- PDF下载量: 1257
- 被引次数: 0
出版历程
- 出版日期: 2011-04-20

Current state and development tendency of tumor therapeutic antibody

Research funding:

摘要

摘要: 单克隆抗体在过去的30多年里经历了快速的发展,从杂交瘤技术的建立起,科学家先后研发出鼠源性、嵌合型、人源化以及全人化抗体技术。目前FDA批准上市的30个抗体中有10个用于肿瘤治疗,抗体治疗也被认为是肿瘤治疗最有效的方法之一。抗体偶联小分子、化疗药物等也成为人们的研究重点,他们展现出比单个治疗更为有效的临床反应。然而,肿瘤治疗抗体仍然存在着体内半衰期短、杀伤作用不够、难以渗透实体瘤、治疗靶点少、治疗成本高等问题。未来抗体研究的重点将是研制低免疫原性、高亲和性、多效价多克隆、更稳定和低成本的抗体。
- 抗体 /
- 肿瘤
Abstract: Monoclonal antibody had achieved huge development in the past thirty years, ranging from hybridoma technology to mouse-derived, mouse/human chimeric, humanized and fully human antibody production technology.So far, thirty monoclonal antibodies have been proved by FDA including ten tumor therapeutic antibodies, and monoclonal antibody has been recognized as one of the most potent therapeutic drugs for tumor.Antibody-drugs conjugated with small molecule, chemotherapeutic drug and so on, which are demonstrated to be more efficient than single drug, have also been the hot spot of antibody research.However, current tumor therapeutic antibodies still have drawbacks including short half-life, unsatisfactory therapeutic potency, solid tumor penetrating difficulty, seldom therapeutic targets and high producing costs to overcome.Future antibody research would focus on these kind of antibodies with lower immunogenicity, higher affinity, multivalent or polyclonal, longer duration and lower costs.
- antibodies /
- neoplasm

HTML全文

参考文献(48)

[1]Zhou H, Mascelli MA.Mechanisms of monoclonal antibody-drug interactions[J].Annu Rev Pharmacol Toxicol, 2011, 51:359-372.

[2]Kohler G, Milstein C.Continuous cultures of fused cellssecreting antibody of predefined specificity[J].Nature, 1975, 256 (5517) :495-497.

[3]Beck A, Wurch T, Bailly C, et al.Strategies and challengesfor the next generation of therapeutic antibodies[J].Nat RevImmunol, 2010, 10 (5) :345-352.

[4]Carter P.Improving the efficacy of antibody-based cancertherapies[J].Nat Rev Cancer, 2001, 1 (2) :118-129.

[5]Kennedy AD, Beum PV, Solga MD, et al.Rituximab infusionpromotes rapid complement depletion and acute CD20loss in chronic lymphocytic leukemia[J].J Immunol, 2004, 172 (5) :3280-3288.

[6]Hagenbeek A, Gadeberg O, Johnson P, et al.First clinicaluse of ofatumumab, a novel fully human anti-CD20monoclonal antibody in relapsed or refractory follicularlymphoma:results of a phase 1/2 trial[J].Blood, 2008, 111 (12) :5486-5495.

[7]Vitetta ES, Uhr JW.Monoclonal antibodies as agonists:anexpanded role for their use in cancer therapy[J].CancerRes, 1994, 54 (20) :5301-5309.

[8]Vuist WM, Levy R, Maloney DG.Lymphoma regressioninduced by monoclonal anti-idiotypic antibodies correlateswith their ability to induce Ig signal transduction and isnot prevented by tumor expression of high levels of bcl-2protein[J].Blood, 1994, 83 (4) :899-906.

[9]Raghavan M, Bonagura VR, Morrison SL, et al.Analysisof the pH dependence of the neonatal Fc receptor/immunoglobulin G interaction using antibody and receptorvariants[J].Biochemistry, 1995, 34 (45) :14649-14657.

[10]Guo MG, Jiang MH, Yang Q, et al.[Gene therapy for ovariancancers by adenovirus-mediated complete antibodygene[J].Zhonghua Yi Xue Za Zhi, 2004, 84 (14) :1147-1151.

[11]Jiang M, Shi W, Zhang Q, et al.Gene therapy usingadenovirus-mediated full-length anti-HER-2 antibody forHER-2 overexpression cancers[J].Clin Cancer Res, 2006, 12 (20 Pt 1) :6179-6185.

[12]Chen J, Su C, Lu Q, et al.Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-celldeletion in mice and nonhuman primate cynomolgusmonkey[J].Mol Cancer Ther, 2008, 7 (6) :1562-1568.

[13]Fang J, Qian JJ, Yi S, et al.Stable antibody expression attherapeutic levels using the 2A peptide[J].Nat Biotechnol, 2005, 23 (5) :584-590.

[14]Fang J, Yi S, Simmons A, et al.An antibody delivery systemfor regulated expression of therapeutic levels of monoclonalantibodies in vivo[J].Mol Ther, 2007, 15 (6) :1153-1159.

[15]Zhang Q, Chen G, Liu X, et al.Monoclonal antibodiesas therapeutic agents in oncology and antibody genetherapy[J].Cell Res, 2007, 17 (2) :89-99.

[16]Ho DT, Wykoff-Clary S, Gross CS, et al.Growth inhibition ofan established A431 xenograft tumor by a full-length anti-EGFR antibody following gene delivery by AAV[J].CancerGene Ther, 2009, 16 (2) :184-194.

[17]Johnson PR, Schnepp BC, Zhang J, et al.Vector-mediatedgene transfer engenders long-lived neutralizing activity andprotection against SIV infection in monkeys[J].Nat Med, 2009, 15 (8) :901-906.

[18]Ryan DA, Mastrangelo MA, Narrow WC, et al.Abeta-directedsingle-chain antibody delivery via a serotype-1 AAV vectorimproves learning behavior and pathology in Alzheimer'sdisease mice[J].Mol Ther, 2010, 18 (8) :1471-1481.

[19]Wang G, Qiu J, Wang R, et al.Persistent expression ofbiologically active anti-HER2 antibody by AAVrh.10-mediatedgene transfer[J].Cancer Gene Ther, 2010, 17 (8) :559-570.

[20]Watanabe M, Boyer JL, Crystal RG.AAVrh.10-mediatedgenetic delivery of bevacizumab to the pleura to providelocal anti-VEGF to suppress growth of metastatic lungtumors[J].Gene Ther, 2010, 17 (8) :1042-1051.

[21]Lv F, Qiu Y, Zhang Y, et al.Adeno-associated virus-mediated anti-DR5 chimeric antibody expressionsuppresses human tumor growth in nude mice[J].CancerLett, 2011, 302 (2) :119-127.

[22]Wang C, Wang M, Liu Y, et al.Administration of adenovirusencoding anti-CD20 antibody gene induces B-cell deletionand alleviates lupus in the BWF1 mouse model[J].IntImmunopharmacol, 2011.[Epub ahead of print]

[23]Cartron G, Dacheux L, Salles G, et al.Therapeutic activityof humanized anti-CD20 monoclonal antibody andpolymorphism in IgG Fc receptor FcgammaRIIIa gene[J].Blood, 2002, 99 (3) :754-758.

[24]Anolik JH, Campbell D, Felgar RE, et al.The relationshipof FcgammaRIIIa genotype to degree of B cell depletionby rituximab in the treatment of systemic lupuserythematosus[J].Arthritis Rheum, 2003, 48 (2) :455-459.

[25]Weng WK, Levy R.Two immunoglobulin G fragment Creceptor polymorphisms independently predict responseto rituximab in patients with follicular lymphoma[J].J ClinOncol, 2003, 21 (21) :3940-3947.

[26]Musolino A, Naldi N, Bortesi B, et al.Immunoglobulin Gfragment C receptor polymorphisms and clinical efficacy oftrastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer[J].J Clin Oncol, 2008, 26 (11) :1789-1796.

[27]Bibeau F, Lopez-Crapez E, Di Fiore F, et al.Impact ofFc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRASmutations on the clinical outcome of patients with metastaticcolorectal cancer treated with cetuximab plus irinotecan[J].J Clin Oncol, 2009, 27 (7) :1122-1129.

[28]Miescher S, Spycher MO, Amstutz H, et al.A singlerecombinant anti-RhD IgG prevents RhD immunization:association of RhD-positive red blood cell clearance ratewith polymorphisms in the FcgammaRIIA and FcgammaIIIAgenes[J].Blood, 2004, 103 (11) :4028-4035.

[29]Salmon JE, Edberg JC, Brogle NL, et al.Allelicpolymorphisms of human Fc gamma receptor IIA andFc gamma receptor IIIB.Independent mechanisms fordifferences in human phagocyte function[J].J Clin Invest, 1992, 89 (4) :1274-1281.

[30]Shields RL, Lai J, Keck R, et al.Lack of fucose on humanIgG1 N-linked oligosaccharide improves binding to humanFcgamma RIII and antibody-dependent cellular toxicity[J].JBiol Chem, 2002, 277 (30) :26733-26740.

[31]Shinkawa T, Nakamura K, Yamane N, et al.The absenceof fucose but not the presence of galactose or bisectingN-acetylglucosamine of human IgG1 complex-typeoligosaccharides shows the critical role of enhancingantibody-dependent cellular cytotoxicity[J].J Biol Chem, 2003, 278 (5) :3466-3473.

[32]Shopes B.A genetically engineered human IgG mutantwith enhanced cytolytic activity[J].J Immunol, 1992, 148 (9) :2918-2922.

[33]Azuma Y, Ishikawa Y, Kawai S, et al.Recombinant humanhexamer-dominant IgM monoclonal antibody to gangliosideGM3 for treatment of melanoma[J].Clin Cancer Res, 2007, 13 (9) :2745-2750.

[34]Idusogie EE, Presta LG, Gazzano-Santoro H, et al.Mappingof the C1q binding site on rituxan, a chimeric antibody with ahuman IgG1 Fc[J].J Immunol, 2000, 164 (8) :4178-4184.

[35]Idusogie EE, Wong PY, Presta LG, et al.Engineeredantibodies with increased activity to recruit complement[J].JImmunol, 2001, 166 (4) :2571-2575.

[36]Natsume A, In M, Takamura H, et al.Engineered antibodiesof IgG1/IgG3 mixed isotype with enhanced cytotoxicactivities[J].Cancer Res, 2008, 68 (10) :3863-3872.

[37]Natsume A, Shimizu-Yokoyama Y, Satoh M, et al.Engineered anti-CD20 antibodies with enhancedcomplement-activating capacity mediate potent anti-lymphoma activity[J].Cancer Sci, 2009, 100 (12) :2411-2418.

[38]Zuckier LS, Chang CJ, Scharff MD, et al.Chimeric human-mouse IgG antibodies with shuffled constant region exonsdemonstrate that multiple domains contribute to in vivo half-life[J].Cancer Res, 1998, 58 (17) :3905-3908.

[39]Zalevsky J, Chamberlain AK, Horton HM, et al.Enhancedantibody half-life improves in vivo activity[J].Nat Biotechnol, 2010, 28 (2) :157-159.

[40]Linke R, Klein A, Seimetz D.Catumaxomab:Clinicaldevelopment and future directions.MAbs, 2010, 2 (2) .[Epubahead of print]

[41]Chames P, Baty D.Bispecific antibodies for cancer therapy:thelight at the end of the tunnel?[J].MAbs, 2009, 1 (6) :539-547.

[42]Swann PG, Tolnay M, Muthukkumar S, et al.Considerationsfor the development of therapeutic monoclonal antibodies[J].Curr Opin Immunol, 2008, 20 (4) :493-499.

[43]Pedersen MW, Jacobsen HJ, Koefoed K, et al.Sym004:a novel synergistic anti-epidermal growth factor receptorantibody mixture with superior anticancer efficacy[J].CancerRes, 2010, 70 (2) :588-597.

[44]Koerber JT, Jang JH, Schaffer DV.DNA shuffling of adeno-associated virus yields functionally diverse viral progeny[J].Mol Ther, 2008, 16 (10) :1703-1709.

[45]Asokan A, Conway JC, Phillips JL, et al.Reengineeringa receptor footprint of adeno-associated virus enablesselective and systemic gene transfer to muscle[J].NatBiotechnol, 2010, 28 (1) :79-82.

[46]Sugahara KN, Teesalu T, Karmali PP, et al.Coadministrationof a tumor-penetrating peptide enhances the efficacy ofcancer drugs[J].Science, 2010, 328 (5981) :1031-1035.

[47]Ciceri F, Bonini C, Stanghellini MT, et al.Infusion ofsuicide-gene-engineered donor lymphocytes after familyhaploidentical haemopoietic stem-cell transplantation forleukaemia (the TK007 trial) :a non-randomised phase I-IIstudy[J].Lancet Oncol, 2009, 10 (5) :489-500.

[48]Tey SK, Dotti G, Rooney CM, et al.Inducible caspase 9suicide gene to improve the safety of allodepleted T cellsafter haploidentical stem cell transplantation[J].Biol BloodMarrow Transplant, 2007, 13 (8) :913-924.

施引文献

资源附件(0)

访问统计