Skip to main content Accessibility help
×
Hostname: page-component-7c8c6479df-94d59 Total loading time: 0 Render date: 2024-03-29T02:32:01.481Z Has data issue: false hasContentIssue false

9 - Mechanisms of Tumor Cell Killing by Therapeutic Antibodies

from PART IV - ANTIBODY EFFECTOR FUNCTION

Published online by Cambridge University Press:  15 December 2009

Melvyn Little
Affiliation:
Affimed Therapeutics AG
Get access

Summary

Since its reemergence following the discovery of monoclonal antibodies in the early 1980s, the field of antibody therapy in cancer has progressed in leaps and bounds. From murine to chimeric, through humanized to fully human, we are now in a situation where, with over 200 antibodies having passed through some kind of clinical testing (Reichert & Valge-Archer, 2007), the monoclonal is now an accepted form of treatment for malignancy. In fact, for some malignancies, most notably non-Hodgkin's lymphoma, monoclonals are routinely used as frontline therapy. As such, we are past the point of asking whether monoclonal therapy works and into the more expansive territory of asking how it works and how we can make it work better.

While antibodies can function to combat a tumor in a number of ways – for example, sequestration of factors essential to survival or growth and stimulation of the immune response – one of the best-studied mechanisms of action is direct tumor cell killing. Here we will begin by looking in detail at the mechanisms by which antibodies can mediate cell killing, and which of these mechanisms is likely to be most important. Subsequently, we will review briefly the possible ways that this cell killing can be increased through the process of protein engineering, several of which will be expanded upon by the authors of subsequent chapters.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Arnould, L., Gelly, M., et al. (2006). “Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?Br J Cancer 94(2): 259–67.CrossRefGoogle Scholar
Barok, M., Isola, J., et al. (2007). “Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance.” Mol Cancer Ther 6(7): 2065–72.CrossRefGoogle ScholarPubMed
Bianco, R., Daniele, G., et al. (2005). “Monoclonal antibodies targeting the epidermal growth factor receptor.” Curr Drug Targets 6(3): 275–87.CrossRefGoogle ScholarPubMed
Borchmann, P., Treml, J.F., et al. (2003). “The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma.” Blood 102(10): 3737–42.CrossRefGoogle ScholarPubMed
Brekke, O.H., Michaelsen, T.E., et al. (1994).“Human IgG isotype-specific amino acid residues affecting complement-mediated cell lysis and phagocytosis.” Eur J Immunol 24(10): 2542–7.CrossRefGoogle ScholarPubMed
Canfield, S.M. and Morrison, S.L. (1991). “The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region.” J Exp Med 173(6): 1483–91.CrossRefGoogle ScholarPubMed
Carlo-Stella, C., Di Nicola, M., et al. (2006). “The anti-human leukocyte antigen-DR monoclonal antibody 1D09C3 activates the mitochondrial cell death pathway and exerts a potent antitumor activity in lymphoma-bearing nonobese diabetic/severe combined immunodeficient mice.” Cancer Res 66(3): 1799–808.CrossRefGoogle ScholarPubMed
Carlotti, E., Palumbo, G.A., et al. (2007). “FcgammaRIIIA and FcgammaRIIA polymorphisms do not predict clinical outcome of follicular non-Hodgkin's lymphoma patients treated with sequential CHOP and rituximab.” Haematologica 92(8): 1127–30.CrossRefGoogle Scholar
Carnahan, J., Stein, R., et al. (2007). “Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab.” Mol Immunol 44(6): 1331–41.CrossRefGoogle ScholarPubMed
Caron, P.C., Lai, L.T., et al. (1995). “Interleukin-2 enhancement of cytotoxicity by humanized monoclonal antibody M195 (anti-CD33) in myelogenous leukemia.” Clin Cancer Res 1(1): 63–70.Google Scholar
Cartron, G., Dacheux, L., et al. (2002). “Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene.” Blood 99(3): 754–8.CrossRefGoogle ScholarPubMed
Chan, H.T., Hughes, D., et al. (2003). “CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts.” Cancer Res 63(17): 5480–9.Google ScholarPubMed
Clynes, R.A., Towers, T.L., et al. (2000). “Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets.” Nat Med 6(4): 443–6.CrossRefGoogle Scholar
Cooley, S., Burns, L.J., et al. (1999). “Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu.” Exp Hematol 27(10): 1533–41.CrossRefGoogle ScholarPubMed
Cragg, M.S. and Glennie, M.J. (2004). “Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents.” Blood 103(7): 2738–43.CrossRefGoogle ScholarPubMed
Dall'Acqua, W.F., Cook, K.E., et al. (2006). “Modulation of the effector functions of a human IgG1 through engineering of its hinge region.” J Immunol 177(2): 1129–38.CrossRefGoogle ScholarPubMed
Danielczyk, A., Stahn, R., et al. (2006). “PankoMab: a potent new generation anti-tumour MUC1 antibody.” Cancer Immunol Immunother 55(11): 1337–47.CrossRefGoogle ScholarPubMed
Deans, J.P., Li, H., et al. (2002). “CD20-mediated apoptosis: signalling through lipid rafts.” Immunology 107(2): 176–82.CrossRefGoogle ScholarPubMed
Di Gaetano, N., Cittera, E., et al. (2003). “Complement activation determines the therapeutic activity of rituximab in vivo.” J Immunol 171(3): 1581–7.CrossRefGoogle ScholarPubMed
Dufner, P., Jermutus, L., et al. (2006). “Harnessing phage and ribosome display for antibody optimisation.” Trends Biotechnol 24(11): 523–9.CrossRefGoogle ScholarPubMed
Duncan, A.R. and Winter, G. (1988). “The binding site for C1q on IgG.” Nature 332(6166): 738–40.CrossRefGoogle ScholarPubMed
Duncan, A.R., Woof, J.M., et al. (1988). “Localization of the binding site for the human high-affinity Fc receptor on IgG.” Nature 332(6164): 563–4.CrossRefGoogle ScholarPubMed
Farag, S.S., Flinn, I.W., et al. (2004). “Fc gamma RIIIa and Fc gamma RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia.” Blood 103(4): 1472–4.CrossRefGoogle Scholar
Fenton, C. and Perry, C.M. (2006). “Spotlight on gemtuzumab ozogamicin in acute myeloid leukaemia.” BioDrugs 20(2): 137–9.CrossRefGoogle ScholarPubMed
Fischer, L., Penack, O., et al. (2006). “The anti-lymphoma effect of antibody-mediated immunotherapy is based on an increased degranulation of peripheral blood natural killer (NK) cells.” Exp Hematol 34(6): 753–9.CrossRefGoogle ScholarPubMed
Galimberti, S., Palumbo, G.A., et al. (2007). “The efficacy of rituximab plus Hyper-CVAD regimen in mantle cell lymphoma is independent of FCgammaRIIIa and FCgammaRIIa polymorphisms.” J Chemother 19(3): 315–21.CrossRefGoogle ScholarPubMed
Gennari, R., Menard, S., et al. (2004). “Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2.” Clin Cancer Res 10(17): 5650–5.CrossRefGoogle ScholarPubMed
Glennie, M.J., French, R.R., et al. (2007). “Mechanisms of killing by anti-CD20 monoclonal antibodies.” Mol Immunol 44(16): 3823–37.CrossRefGoogle ScholarPubMed
Golay, J., Cittera, E., et al. (2006). “The role of complement in the therapeutic activity of rituximab in a murine B lymphoma model homing in lymph nodes.” Haematologica 91(2): 176–83.Google Scholar
Golay, J., Lazzari, M., et al. (2001). “CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59.” Blood 98(12): 3383–9.CrossRefGoogle ScholarPubMed
Golay, J., Manganini, M., et al. (2003). “Rituximab-mediated antibody-dependent cellular cytotoxicity against neoplastic B cells is stimulated strongly by interleukin-2.” Haematologica 88(9): 1002–12.Google ScholarPubMed
Golay, J., Zaffaroni, L., et al. (2000). “Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis.” Blood 95(12): 3900–8.Google ScholarPubMed
Gong, Q., Ou, Q. et al. (2005). “Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy.” J Immunol 174(2): 817–26.CrossRefGoogle ScholarPubMed
Hamaguchi, Y., Xiu, Y., et al. (2006). “Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy.” J Exp Med 203(3): 743–53.CrossRefGoogle ScholarPubMed
Hammond, P.W., Vafa, O., et al. (2005). “A humanized anti-CD30 monoclonal antibody, XmAbTM2513, with enhanced in vitro potency against CD30-positive lymphomas mediated by high affinity Fc-receptor binding.” The American Society of Hematology 47th Annual Meeting and Exposition.Google Scholar
Harjunpaa, A., Junnikkala, S., et al. (2000). “Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms.” Scand J Immunol 51(6): 634–41.CrossRefGoogle ScholarPubMed
Hernandez-Ilizaliturri, F.J., Jupudy, V., et al. (2003). “Neutrophils contribute to the biological antitumor activity of rituximab in a non-Hodgkin's lymphoma severe combined immunodeficiency mouse model.” Clin Cancer Res 9(16 Pt 1): 5866–73.Google Scholar
Hinoda, Y., Sasaki, S., et al. (2004). “Monoclonal antibodies as effective therapeutic agents for solid tumors.” Cancer Sci 95(8): 621–5.CrossRefGoogle ScholarPubMed
Hofmeister, J.K., Cooney, D., et al. (2000). “Clustered CD20 induced apoptosis: src-family kinase, the proximal regulator of tyrosine phosphorylation, calcium influx, and caspase 3-dependent apoptosis.” Blood Cells Mol Dis 26(2): 133–43.CrossRefGoogle ScholarPubMed
Hoogenboom, H.R. (2005). “Selecting and screening recombinant antibody libraries.” Nat Biotechnol 23(9): 1105–16.CrossRefGoogle ScholarPubMed
Idusogie, E.E., Presta, L.G., et al. (2000). “Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc.” J Immunol 164(8): 4178–84.CrossRefGoogle ScholarPubMed
Jefferis, R. (2007). “Antibody therapeutics: isotype and glycoform selection.” Expert Opin Biol Ther 7(9): 1401–13.CrossRefGoogle ScholarPubMed
Kennedy, A.D., Beum, P.V., et al. (2004). “Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia.” J Immunol 172(5): 3280–8.CrossRefGoogle ScholarPubMed
Kimura, H., Sakai, K., et al. (2007). “Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor.” Cancer Sci 98(8): 1275–80.CrossRefGoogle ScholarPubMed
Kreitman, R.J. and Pastan, I. (2006). “BL22 and lymphoid malignancies.” Best Pract Res Clin Haematol 19(4): 685–99.CrossRefGoogle ScholarPubMed
Lazar, G.A., Dang, W., et al. (2006). “Engineered antibody Fc variants with enhanced effector function.” Proc Natl Acad Sci USA 103(11): 4005–10.CrossRefGoogle ScholarPubMed
Lefebvre, M.L., Krause, S.W., et al. (2006). “Ex vivo-activated human macrophages kill chronic lymphocytic leukemia cells in the presence of rituximab: mechanism of antibody-dependent cellular cytotoxicity and impact of human serum.” J Immunother (1997) 29(4): 388–97.CrossRefGoogle ScholarPubMed
Lopes de Menezes, D.E., Denis-Mize, K., et al. (2007). “Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.” J Immunother (1997) 30(1): 64–74.CrossRefGoogle ScholarPubMed
Lund, J., Pound, J.D., et al. (1992). “Multiple binding sites on the CH2 domain of IgG for mouse Fc gamma R11.” Mol Immunol 29(1): 53–9.CrossRefGoogle ScholarPubMed
Manches, O., Lui, G., et al. (2003). “In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas.” Blood 101(3): 949–54.CrossRefGoogle ScholarPubMed
Marshall, J. (2006). “Clinical implications of the mechanism of epidermal growth factor receptor inhibitors.” Cancer 107(6): 1207–18.CrossRefGoogle ScholarPubMed
Mitrovic, Z., Aurer, I., et al. (2007). “FCgammaRIIIA and FCgammaRIIA polymorphisms are not associated with response to rituximab and CHOP in patients with diffuse large B-cell lymphoma.” Haematologica 92(7): 998–9.CrossRefGoogle Scholar
Morgan, A., Jones, N.D., et al. (1995). “The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding.” Immunology 86(2): 319–24.Google ScholarPubMed
Nimmerjahn, F. and Ravetch, J.V. (2005). “Divergent immunoglobulin g subclass activity through selective Fc receptor binding.” Science 310(5753): 1510–2.CrossRefGoogle ScholarPubMed
Niwa, R., Natsume, A., et al. (2005). “IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides.” J Immunol Methods 306(1–2): 151–60.CrossRefGoogle ScholarPubMed
Nuutila, J., Hohenthal, U., et al. (2007). “Simultaneous quantitative analysis of FcgammaRI (CD64) expression on neutrophils and monocytes: A new, improved way to detect infections.” J Immunol Methods 228(1–2): 189–200.CrossRefGoogle Scholar
Pathan, N.I., Chu, P., et al. (2007). “Mediation of apoptosis by and anti-tumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines.” Blood 111(3): 1594–1602.CrossRefGoogle Scholar
Prang, N., Preithner, S., et al. (2005). “Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines.” Br J Cancer 92(2): 342–9.CrossRefGoogle ScholarPubMed
Press, O.W., Farr, A.G., et al. (1989). “Endocytosis and degradation of monoclonal antibodies targeting human B-cell malignancies.” Cancer Res 49(17): 4906–12.Google ScholarPubMed
Pukac, L., Kanakaraj, P., et al. (2005). “HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo.” Br J Cancer 92(8): 1430–41.CrossRefGoogle ScholarPubMed
Radaev, S., Motyka, S., et al. (2001). “The structure of a human type III Fcgamma receptor in complex with Fc.” J Biol Chem 276(19): 16469–77.CrossRefGoogle ScholarPubMed
Reichert, J.M. and Valge-Archer, V.E. (2007). “Development trends for monoclonal antibody cancer therapeutics.” Nat Rev Drug Discov 6(5): 349–56.CrossRefGoogle ScholarPubMed
Sensel, M.G., Kane, L.M., et al. (1997). “Amino acid differences in the N-terminus of C(H)2 influence the relative abilities of IgG2 and IgG3 to activate complement.” Mol Immunol 34(14): 1019–29.CrossRefGoogle ScholarPubMed
Shan, D., Ledbetter, J.A., et al. (2000). “Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells.” Cancer Immunol Immunother 48(12): 673–83.CrossRefGoogle ScholarPubMed
Shields, R.L., Namenuk, A.K., et al. (2001). “High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R.” J Biol Chem 276(9): 6591–604.CrossRefGoogle Scholar
Siberil, S., Dutertre, C.A., et al. (2007). “FcgammaR: The key to optimize therapeutic antibodies?Crit Rev Oncol Hematol 62(1): 26–33.CrossRefGoogle ScholarPubMed
Sieber, T., Schoeler, D., et al. (2003). “Selective internalization of monoclonal antibodies by B-cell chronic lymphocytic leukaemia cells.” Br J Haematol 121(3): 458–61.CrossRefGoogle ScholarPubMed
Sondermann, P., Huber, R., et al. (2000). “The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex.” Nature 406(6793): 267–73.CrossRefGoogle ScholarPubMed
Sondermann, P., Kaiser, J., et al. (2001). “Molecular basis for immune complex recognition: a comparison of Fc-receptor structures.” J Mol Biol 309(3): 737–49.CrossRefGoogle ScholarPubMed
Stavenhagen, J.B., Gorlatov, S., et al. (2007). “Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors.” Cancer Res 67(18): 8882–90.CrossRefGoogle ScholarPubMed
Suzuki, E., Niwa, R., et al. (2007). “A nonfucosylated anti-HER2 antibody augments antibody-dependent cellular cytotoxicity in breast cancer patients.” Clin Cancer Res 13(6): 1875–82.CrossRefGoogle ScholarPubMed
Tai, Y.T., Li, X., et al. (2005). “Human anti-CD40 antagonist antibody triggers significant antitumor activity against human multiple myeloma.” Cancer Res 65(13): 5898–906.CrossRefGoogle ScholarPubMed
Tai, Y.T., Li, X.F., et al. (2005). “Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications.” Cancer Res 65(24): 11712–20.CrossRefGoogle ScholarPubMed
Takeda, K., Stagg, J., et al. (2007). “Targeting death-inducing receptors in cancer therapy.” Oncogene 26(25): 3745–57.CrossRefGoogle ScholarPubMed
Tang, Y., Lou, J., et al. (2007). “Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen.” J Immunol 179(5): 2815–23.CrossRefGoogle ScholarPubMed
Tao, M.H., Canfield, S.M., et al. (1991). “The differential ability of human IgG1 and IgG4 to activate complement is determined by the COOH-terminal sequence of the CH2 domain.” J Exp Med 173(4): 1025–8.CrossRefGoogle ScholarPubMed
Tao, M.H., Smith, R.I., et al. (1993). “Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.” J Exp Med 178(2): 661–7.CrossRefGoogle ScholarPubMed
Teeling, J.L., Mackus, W.J., et al. (2006). “The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20.” J Immunol 177(1): 362–71.CrossRefGoogle ScholarPubMed
Thommesen, J.E., Michaelsen, T.E., et al. (2000). “Lysine 322 in the human IgG3 C(H)2 domain is crucial for antibody dependent complement activation.” Mol Immunol 37(16): 995–1004.CrossRefGoogle ScholarPubMed
Treon, S.P., Mitsiades, C., et al. (2001). “Tumor Cell Expression of CD59 Is Associated With Resistance to CD20 Serotherapy in Patients With B-Cell Malignancies.” J Immunother 24(3): 263–271.CrossRefGoogle ScholarPubMed
Uchida, J., Hamaguchi, Y., et al. (2004). “The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.” J Exp Med 199(12): 1659–69.CrossRefGoogle ScholarPubMed
Valabrega, G., Montemurro, F., et al. (2007). “Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer.” Ann Oncol 18(6): 977–84.CrossRefGoogle ScholarPubMed
Winkel, J.G. and Capel, P.J. (1993). “Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications.” Immunol Today 14(5): 215–21.CrossRefGoogle ScholarPubMed
Kolk, L.E., Haas, M., et al. (2002). “Analysis of CD20-dependent cellular cytotoxicity by G-CSF-stimulated neutrophils.” Leukemia 16(4): 693–9.CrossRefGoogle ScholarPubMed
Kolk, L.E., Evers, L.M., et al. (2002). “CD20-induced B cell death can bypass mitochondria and caspase activation.” Leukemia 16(9): 1735–44.CrossRefGoogle ScholarPubMed
Kolk, L.E., Grillo-Lopez, A.J., et al. (2001). “Complement activation plays a key role in the side-effects of rituximab treatment.” Br J Haematol 115(4): 807–11.CrossRefGoogle Scholar
Meerten, T., Rijn, R.S., et al. (2006). “Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity.” Clin Cancer Res 12(13): 4027–35.CrossRefGoogle ScholarPubMed
Wahl, A.F., Klussman, K., et al. (2002). “The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease.” Cancer Res 62(13): 3736–42.Google ScholarPubMed
Weng, W.K. and Levy, R. (2001). “Expression of complement inhibitors CD46, CD55, and CD59 on tumor cells does not predict clinical outcome after rituximab treatment in follicular non-Hodgkin lymphoma.” Blood 98(5): 1352–7.CrossRefGoogle Scholar
Weng, W.K. and Levy, R. (2003). “Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma.” J Clin Oncol 21(21): 3940–7.CrossRefGoogle ScholarPubMed
Wong, S.F. (2005). “Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer.” Clin Ther 27(6): 684–94.Google Scholar
Woof, J.M., Partridge, L.J., et al. (1986). “Localisation of the monocyte-binding region on human immunoglobulin G.” Mol Immunol 23(3): 319–30.CrossRefGoogle ScholarPubMed
Xia Tong, G.V.G., Long, Li, O'Brien, Susan, Younes, Anas, Luqman, Mohammad(2004). “In Vitro Activity of a Novel Fully Human Anti-CD40 Antibody CHIR-12.12 in Chronic Lymphocytic Leukemia: Blockade of CD40 Activation and Induction of ADCC.” 46th ASH Annual Meeting.Google Scholar
Xu, Y., Oomen, R., et al. (1994). “Residue at position 331 in the IgG1 and IgG4 CH2 domains contributes to their differential ability to bind and activate complement.” J Biol Chem 269(5): 3469–74.Google ScholarPubMed
Yazawa, N., Hamaguchi, Y., et al. (2005). “Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease.” Proc Natl Acad Sci USA 102(42): 15178–83.CrossRefGoogle ScholarPubMed
Zhang, W., Gordon, M., et al. (2007). “FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.” J Clin Oncol 25(24): 3712–8.CrossRefGoogle ScholarPubMed
Zhukovsky, E., Chu, S., Bernett, M., Karki, S., Dang, W., Hammond, P., Edler, C., Polder, N., Chan, C., Jacinto, J., Desjarlais, J. (2007). “XmAb Fc engineered anti-CD19 monoclonal antibodies with enhanced in vitro efficacy against multiple lymphoma cell lines.” Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I 25(18S) (June 20 Supplement): 3021.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×