Review Article | Published:

Building better monoclonal antibody-based therapeutics

Nature Reviews Cancer volume 15, pages 361370 (2015) | Download Citation


For 20 years, monoclonal antibodies (mAbs) have been a standard component of cancer therapy, but there is still much room for improvement. Efforts continue to build better cancer therapeutics based on mAbs. Anticancer mAbs function through various mechanisms, including directly targeting the malignant cells, modifying the host response, delivering cytotoxic moieties and retargeting cellular immunity towards the malignant cells. Characteristics of mAbs that affect their efficacy include antigen specificity, overall structure, affinity for the target antigen and how a mAb component is incorporated into a construct that can trigger target cell death. This Review discusses the various approaches to using mAb-based therapeutics to treat cancer and the strategies used to take advantage of the unique potential of each approach, and provides examples of current mAb-based treatments.

Key points

  • Monoclonal antibody (mAb)-based therapeutics are now standard in the treatment of cancer, and the numbers and varieties of clinically applicable mAb-based approaches continue to grow.

  • Effective mAb-based treatments of cancer include directly targeting the cancer, altering the host response to the cancer, delivering cytotoxic moieties to the cancer and retargeting T cells towards the cancer.

  • mAb-based treatments that directly target the cancer mediate their effects through direct signalling, antibody-dependent cellular cytotoxicity and complement-mediated lysis. Differentiating which of these mechanisms is most important for a given mAb can be difficult but is important when working to identify better mAb-based treatments.

  • mAb-based treatments that alter the host response can alter tumour angiogenesis or the T cell response through T cell checkpoint blockade. Checkpoint-blockade mAbs are showing particular promise.

  • mAb-based treatments that deliver cytotoxic agents to the cancer include radioimmunotherapy and antibody–drug conjugates (ADCs). ADCs are complex because of the need to match the target cancer to the right mAb, linker and drug, but early results are promising and many new ADCs are in development.

  • mAb-based treatments that retarget T cells towards cancer include bispecific antibodies and chimeric antigen receptor T cells. Both approaches are logistically challenging but have demonstrated exciting early results, particularly in B cell malignancies.

  • Each of these approaches has advantages and disadvantages that need to be considered in their development and evaluation.

  • Rapid progress is taking place in the development of new agents and the testing of new approaches, both alone and in combination, in each of these areas.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Collected Studies on Immunity 1st edn (J. Wiley & Sons, 1906).

  2. 2.

    & Passive immunity in prevention and treatment of infectious diseases. Clin. Microbiol. Rev. 13, 602–614 (2000).

  3. 3.

    & Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495 (1975). This landmark publication outlines how to produce mAbs, as well as their therapeutic potential.

  4. 4.

    From the structure of antibodies to the diversification of the immune response. Nobel lecture, 8 December 1984. Biosci. Rep. 5, 275–297 (1985).

  5. 5.

    & The clusters of differentiation (CD) defined by the First International Workshop on Human Leucocyte Differentiation Antigens. Hum. Immunol. 11, 1–10 (1984).

  6. 6.

    & Overview of monoclonal antibodies in the diagnosis and therapy of cancer. Cancer Invest. 9, 195–209 (1991).

  7. 7.

    et al. A clinical trial of anti-idiotype therapy for B cell malignancy. Blood 65, 1349–1363 (1985). This early clinical trial demonstrated the potential efficacy of mAb-based therapy and many of the challenges associated with it.

  8. 8.

    et al. Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc. Natl Acad. Sci. USA 86, 4220–4224 (1989).

  9. 9.

    et al. Idec-C2b8 (Rituximab) anti-CD20 monoclonal antibody therapy patients with relapsed low-grade non-Hodgkins lymphoma. Blood 90, 2188–2195 (1997). This article details the first clinical trial to demonstrate the clear clinical efficacy of a chimeric human–murine mAb.

  10. 10.

    , & Antibody therapy of cancer. Nature Rev. Cancer 12, 278–287 (2012).

  11. 11.

    et al. Monoclonal antibody therapy of B cell lymphoma: signaling activity on tumor cells appears more important than recruitment of effectors. J. Immunol. 161, 3176–3185 (1998).

  12. 12.

    Of mice and mechanisms: identifying the role of complement in monoclonal antibody-based immunotherapy. Haematologica 91, 146a (2006).

  13. 13.

    , , , & Fc receptors are required in passive and active immunity to melanoma. Proc. Natl Acad. Sci. USA 95, 652–656 (1998).

  14. 14.

    et al. Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation. Blood 112, 4170–4177 (2008).

  15. 15.

    , & Apoptosis of malignant human B cells by ligation of CD20 monoclonal antibodies. Blood 91, 1644–1652 (1998).

  16. 16.

    , , , & The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism. Blood 99, 1314–1319 (2002).

  17. 17.

    Rituximab: mechanism of action. Semin. Hematol. 47, 115–123 (2010).

  18. 18.

    , & Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells. Cancer Immunol. Immunother. 48, 673–683 (2000).

  19. 19.

    , & Targeting HER2 for the treatment of breast cancer. Annu. Rev. Med. 66, 111–128 (2015).

  20. 20.

    & Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials. BMC Med. 12, 132 (2014).

  21. 21.

    & Untangling the ErbB signalling network. Nature Rev. Mol. Cell Biol. 2, 127–137 (2001).

  22. 22.

    & The ERBB network: at last, cancer therapy meets systems biology. Nature Rev. Cancer 12, 553–563 (2012).

  23. 23.

    et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5, 317–328 (2004).

  24. 24.

    et al. Differential signaling by an anti-p185HER2 antibody and heregulin. Cancer Res. 60, 3522–3531 (2000).

  25. 25.

    et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, Phase 3 study. Lancet Oncol. 14, 461–471 (2013).

  26. 26.

    & Snake venom in relation to haemolysis, bacteriolysis, and toxicity. J. Exp. Med. 6, 277–301 (1902).

  27. 27.

    & Complement and cellular cytotoxicity in antibody therapy of cancer. Expert Opin. Biol. Ther. 8, 759–768 (2008).

  28. 28.

    et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J. Immunol. 177, 362–371 (2006).

  29. 29.

    et al. Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood 117, 4519–4529 (2011).

  30. 30.

    , , , & Engineered anti-CD20 antibodies with enhanced complement-activating capacity mediate potent anti-lymphoma activity. Cancer Sci. 100, 2411–2418 (2009).

  31. 31.

    et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115, 4393–4402 (2010).

  32. 32.

    et al. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX. J. Immunol. 183, 749–758 (2009).

  33. 33.

    et al. Loss of CD20 and bound CD20 antibody from opsonized B cells occurs more rapidly because of trogocytosis mediated by Fc receptor-expressing effector cells than direct internalization by the B cells. J. Immunol. 187, 3438–3447 (2011).

  34. 34.

    et al. Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model. Blood 114, 5322–5330 (2009).

  35. 35.

    et al. Rituximab-dependent cytotoxicity by natural killer cells: influence of FCGR3A polymorphism on the concentration–effect relationship. Cancer Res. 64, 4664–4669 (2004).

  36. 36.

    , , & 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. 29, 388–397 (2006).

  37. 37.

    et al. Neutrophils contribute to the biological antitumor activity of rituximab in a non-Hodgkin's lymphoma severe combined immunodeficiency mouse model. Clin. Cancer Res. 9, 5866–5873 (2003).

  38. 38.

    & Neutrophils: “neu players” in antibody therapy? Blood 122, 3093–3094 (2013).

  39. 39.

    , , & Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nature Med. 6, 443–446 (2000). This important publication illustrates the importance of both activating and inhibitory FcRs in mediating the antitumour effects of mAbs.

  40. 40.

    & CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells. J. Immunol. Methods 304, 88–99 (2005).

  41. 41.

    , & The high-affinity FcγRI on PMN: regulation of expression and signal transduction. Immunology 92, 544–552 (1997).

  42. 42.

    , , & Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol. Immunol. 44, 3823–3837 (2007).

  43. 43.

    , & Complement in monoclonal antibody therapy of cancer. Immunol. Res. 59, 203–210 (2014).

  44. 44.

    , , & NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement. Blood 111, 1456–1463 (2008).

  45. 45.

    et al. Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J. Clin. Invest. 117, 1361–1369 (2007).

  46. 46.

    et al. Inhibitory FcγRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity. Blood 123, 669–677 (2014).

  47. 47.

    , & Trastuzumab in the treatment of metastatic breast cancer: anticancer therapy versus cardiotoxicity. Circulation 102, 272–274 (2000).

  48. 48.

    et al. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res. 40, 3147–3154 (1980).

  49. 49.

    et al. HER2 monoclonal antibodies that do not interfere with receptor heterodimerization-mediated signaling induce effective internalization and represent valuable components for rational antibody–drug conjugate design. mAbs 6, 392–402 (2014).

  50. 50.

    et al. Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab. Blood 108, 2648–2654. (2006).

  51. 51.

    et al. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101. Mol. Cancer Ther. 10, 178–185 (2011).

  52. 52.

    et al. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood 119, 5126–5132 (2012).

  53. 53.

    et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the Phase 1/2 GAUGUIN study. Blood 124, 2196–2202 (2014).

  54. 54.

    et al. Recombinant dimeric IgA antibodies against the epidermal growth factor receptor mediate effective tumor cell killing. J. Immunol. 186, 3770–3778 (2011).

  55. 55.

    , & Approaching untargetable tumor-associated antigens with antibodies. Oncoimmunology 2, e24678 (2013).

  56. 56.

    et al. A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in human BCR–ABL+ leukemias. Blood 123, 3296–3304 (2014).

  57. 57.

    et al. An anti-PR1/HLA-A2 T-cell receptor-like antibody mediates complement-dependent cytotoxicity against acute myeloid leukemia progenitor cells. Blood 117, 4262–4272 (2011).

  58. 58.

    Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186 (1971). This article is a description of the potential therapeutic impact of altering angiogenesis.

  59. 59.

    , , & Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nature Rev. Drug Discov. 3, 391–400 (2004).

  60. 60.

    & Controlling escape from angiogenesis inhibitors. Nature Rev. Cancer 12, 699–709 (2012).

  61. 61.

    , & Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis. PLoS ONE 6, e22681 (2011).

  62. 62.

    et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J. Clin. Oncol. 28, 1963–1972 (2010).

  63. 63.

    , & Angiogenesis modulation in cancer research: novel clinical approaches. Nature Rev. Drug Discov. 1, 415–426 (2002).

  64. 64.

    The blockade of immune checkpoints in cancer immunotherapy. Nature Rev. Cancer 12, 252–264 (2012).

  65. 65.

    , , , & Immune modulation in cancer with antibodies. Annu. Rev. Med. 65, 185–202 (2014).

  66. 66.

    , , & Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr. Opin. Immunol. 18, 206–213 (2006).

  67. 67.

    et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010). This article documents a successful clinical trial of checkpoint blockade in cancer.

  68. 68.

    et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364, 2517–2526 (2011).

  69. 69.

    , , , & Ipilimumab. Nature Rev. Drug Discov. 10, 411–412 (2011).

  70. 70.

    et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455–2465 (2012).

  71. 71.

    et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a Phase 1 trial. Lancet 384, 1109–1117 (2014).

  72. 72.

    et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369, 122–133 (2013).

  73. 73.

    et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012).

  74. 74.

    et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 372, 311–319 (2015). This article describes an early phase clinical trial that demonstrates how an enhanced understanding of the immune response can lead to the development of a new therapeutic approach.

  75. 75.

    The history and progress of serologic immunotherapy and radiodiagnosis. Radiology 118, 219–223 (1976).

  76. 76.

    et al. Radiolabeled antibody in the treatment of primary and metastatic liver malignancies. Recent Results Cancer Res. 1986, 100307–100314 (1986).

  77. 77.

    et al. Clinical radioimmunotherapy — the role of radiobiology. Nature Rev. Clin. Oncol. 8, 720–734 (2011).

  78. 78.

    , & Optimization of radioimmunotherapy of solid tumors: biological impediments and their modulation. Clin. Cancer Res. 13, 1374–1382 (2007).

  79. 79.

    et al. Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J. Clin. Oncol. 23, 1538–1547 (2005).

  80. 80.

    et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J. Clin. Oncol. 20, 2453–2463 (2002).

  81. 81.

    et al. Radioimmunotherapy of B-cell lymphoma with 131I anti-B1 (anti-CD20) antibody. N. Engl. J. Med. 329, 459–465 (1993). This early clinical trial demonstrated the efficacy of radioimmunotherapy.

  82. 82.

    et al. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma. Blood 123, 2953–2959 (2014).

  83. 83.

    et al. A Phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma. Am. J. Hematol. 53, 211–217 (2012).

  84. 84.

    Can α-radioimmunotherapy increase efficacy for the systemic control of cancer? Immunotherapy 3, 455–458 (2011).

  85. 85.

    & Astatine-211: production and availability. Curr. Radiopharm. 4, 177–185 (2011).

  86. 86.

    & Actinium-225 in targeted α-particle therapeutic applications. Curr. Radiopharm. 4, 306–320 (2011).

  87. 87.

    & Immunotoxins in the therapy of cancer: from bench to clinic. Pharmacol. Ther. 63, 209–234 (1994).

  88. 88.

    , & Antibody–drug conjugates. Nature Rev. Drug Discov. 12, 259–260 (2013).

  89. 89.

    & Picking the optimal target for antibody–drug conjugates. American Society of Clinical Oncology , (2013).

  90. 90.

    et al. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res. 53, 3336–3342 (1993).

  91. 91.

    et al. Antineoplastic agents 337. Synthesis of dolastatin 10 structural modifications. Anticancer Drug Des. 10, 529–544 (1995).

  92. 92.

    et al. Maytansine, a novel antileukemic ansa macrolide from Maytenus ovatus. J. Am. Chem. Soc. 94, 1354–1356 (1972).

  93. 93.

    et al. Synthesis of novel C2-aryl pyrrolobenzodiazepines (PBDs) as potential antitumour agents. Chem. Commun. 21, 1764–1765 (2002).

  94. 94.

    & Antibody–drug conjugates in cancer therapy. Annu. Rev. Med. 64, 15–29 (2013).

  95. 95.

    et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody–drug conjugates. Nature Biotech. 30, 184–189 (2012).

  96. 96.

    et al. Results of a pivotal Phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J. Clin. Oncol. 30, 2183–2189 (2012).

  97. 97.

    et al. Durable remissions in a pivotal Phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood 125, 1236–1243 (2015).

  98. 98.

    et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367, 1783–1791 (2012). This clinical trial demonstrated the potential efficacy of an ADC in a solid tumour.

  99. 99.

    Maturing antibody–drug conjugate pipeline hits 30. Nature Rev. Drug Discov. 12, 329–332 (2013).

  100. 100.

    et al. Phase I/II study of the antibody–drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer. J. Clin. Oncol. 32, 3619–3625 (2014).

  101. 101.

    et al. Phase I/II study of the antibody–drug conjugate glembatumumab vedotin in patients with advanced melanoma. J. Clin. Oncol. 32, 3659–3666 (2014).

  102. 102.

    et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N. Engl. J. Med. 363, 1324–1334 (2010).

  103. 103.

    et al. Antitumor activity of hu14.18-IL2 in patients with relapsed/refractory neuroblastoma: a Children's Oncology Group (COG) Phase II study. J. Clin. Oncol. 28, 4969–4975 (2010).

  104. 104.

    et al. Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma. J. Clin. Oncol. 32, 1445–1452 (2014).

  105. 105.

    , & Bispecific antibodies in cancer therapy. Curr. Opin. Immunol. 11, 558–562 (1999).

  106. 106.

    et al. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leukemia Lymphoma 50, 886–891 (2009).

  107. 107.

    et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J. Clin. Oncol. 29, 2493–2498 (2011). This clinical trial demonstrated the potential efficacy of bispecific antibody therapy.

  108. 108.

    , , , & Chimeric antigen receptor therapy for cancer. Annu. Rev. Med. 65, 333–347 (2014).

  109. 109.

    , , & T-cell therapy at the threshold. Nature Biotech. 30, 611–614 (2012).

  110. 110.

    et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a Phase 1 dose-escalation trial. Lancet 385, 517–528 (2014).

  111. 111.

    et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371, 1507–1517 (2014).

  112. 112.

    et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci. Transl Med. 3, 95ra73 (2011). This early demonstration of the potential of CAR T cells included the potential to develop CAR T memory cells.

  113. 113.

    , , & Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 20, 119–122 (2014).

  114. 114.

    CAR-T cell therapy seeks strategies to harness cytokine storm. Nature Biotech. 32, 604 (2014).

Download references


The author would like to acknowledge support from the US National Institutes of Health grants P30 CA86862 and P50 CA97274.

Author information


  1. Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 5970Z-JPP, Iowa City, Iowa 52242, USA.

    • George J. Weiner


  1. Search for George J. Weiner in:

Competing interests

The author declares no competing financial interests.

Corresponding author

Correspondence to George J. Weiner.


Cluster of differentiation numbers

Numbers assigned to cell surface molecules on the basis of immunophenotyping. They are often used to identify different monoclonal antibodies that bind to the same antigen.

Transmembrane signalling

The process by which an extracellular signal, mediated by a natural ligand or an alternative agent such as a monoclonal antibody, binds to a membrane receptor and generates an intracellular signal that can affect a broad range of cellular functions, including cell growth, cell differentiation and cell death.

Complement-mediated cytotoxicity

(CMC). Also known as complement-dependent cytotoxicity. Cell death resulting from the activation of the complement cascade by a monoclonal antibody that leads to the formation of a membrane attack complex on the surface of the cell.

Antibody-dependent cellular cytotoxicity

(ADCC). Lysis of a target cell by an immune effector cell (such as a natural killer cell, monocyte, macrophage or granulocyte) induced by the recognition of an antibody bound to the surface of the target cell.

Fc receptors

(FcRs). A family of protein receptors specific for an epitope on the constant region of an antibody. When FcRs on immune effector cells come into contact with an antibody-coated target cell, this can result in immune effector cell activation (FcRs with immunoreceptor tyrosine-based activation motifs (ITAMs)) or inhibition (FcRs with immunoreceptor tyrosine-based inhibitory motifs (ITIMs)).

Complement fixation

Initiation of the complement cascade by an antibody bound to an antigen. It can lead to complement-mediated cytotoxicity of the target cell, as well as other complex effects mediated by the activation of various complement components.

mAb isotype

The subtype of a monoclonal antibody (mAb) based on the amino acid sequence of the constant region. Isotypes (IgG1, IgG2, IgG3 and IgG4) vary in their ability to mediate antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity.


The post-translational attachment of a carbohydrate moiety to a protein. The Fc region of immunoglobulin G includes carbohydrate moieties. Altering the enzymes responsible for glycosylation in a cell line that produces a monoclonal antibody (mAb) can alter the glycosylation of the mAb, thereby altering its ability to activate immune effector cells.


The process by which a target is marked for phagocytosis or for destruction by phagocytes. This term is often used to describe phagocytosis of microbial pathogens. In the case of monoclonal antibody therapy of cancer, the target is a cancer cell.

Checkpoint blockade

Inhibitory pathways limit T cell activation in order to maintain self-tolerance and prevent autoimmunity. Checkpoint blockade involves blocking these inhibitory pathways, and thereby allowing for to a more robust T cell response.

Breakthrough therapy designation

US Food and Drug Administration (FDA) designation if a new drug is intended to treat a serious or life-threatening disease and preliminary clinical evidence suggests that it provides a substantial improvement over existing therapies.

Bispecific antibody

(Also known as bifunctional antibody). An engineered monoclonal antibody (mAb) that is composed of fragments of two different mAbs that bind to two different antigens. In cancer therapy, it typically binds to an activating antigen on an immune effector cell with one arm and to a tumour-associated antigen on a cancer cell with the other arm, thereby retargeting the immune effector cell towards the target cancer cell.

Chimeric antigen receptor

(CAR). An engineered receptor that grafts an alternative specificity onto an immune effector cell, most often a T cell. Most of the current constructs for engineered receptors include a single-chain monoclonal antibody variable region that recognizes the target cell and is linked to activating transmembrane domains that activate the T cell when it comes into contact with a target cell.

About this article

Publication history



Further reading