Postulated mechanisms of resistance of B-cell non-Hodgkin lymphoma to rituximab treatment regimens: Strategies to overcome resistance

Seminars in Oncology

Volumn 41, Issue 5, 2014, Pages 667-677

  Bonavida, Benjamin ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BAY 7805; BORTEZOMIB; CD20 ANTIGEN; DEHYDROXYMETHYLEPOXYQUINOMICIN; DEXAMETHASONE; EPRATUZUMAB; FAS LIGAND; GRANULOCYTE COLONY STIMULATING FACTOR; HISTONE DEACETYLASE INHIBITOR; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LENALIDOMIDE; MITOGEN ACTIVATED PROTEIN KINASE P38; OBINUTUZUMAB; OBLIMERSEM; OFATUMUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN KINASE B; RAF PROTEIN; RITUXIMAB; ROMIDEPSIN; TEMSIROLIMUS; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; VALPROIC ACID; MONOCLONAL ANTIBODY;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; APOPTOSIS; B CELL LYMPHOMA; CANCER RESISTANCE; CHEMOSENSITIZATION; COMPLEMENT DEPENDENT CYTOTOXICITY; DRUG EFFICACY; DRUG POTENTIATION; DRUG RESPONSE; HUMAN; MOLECULAR PATHOLOGY; NONHODGKIN LYMPHOMA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; ANIMAL; DRUG EFFECTS; DRUG RESISTANCE; LYMPHOMA, B-CELL;

ANIMALS; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; LYMPHOMA, B-CELL; RITUXIMAB;

EID: 84909634201     PISSN: 00937754     EISSN: 15328708     Source Type: Journal    
DOI: 10.1053/j.seminoncol.2014.08.006     Document Type: Article

References (87)

1. Lippert TH, Ruoff HJ, Volm M. Intrinsic and acquired drug resistance in malignant tumors. The main reason for therapeutic failure. Arzneimittelforschung. 2008;58:261-4.
2. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibodu of predefined specificity. Nature. 1975;256:495-7.
3. Reff ME, Carner K, Chambers KS, Chinn PC, Leonar JE, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435-45.
4. Newman R, Alberts J, Anderson D, Carner K, Heard C, Norton F, et al. "Primatization" of recombinant antibodies for immunotherapy of human diseases: a macaque/human chimeric antibody against human CD4. Biotechnology. 1992;10:1455-60.
5. Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997;90:2188-95.
6. Davis TA, White CA, Grillo-Lopez AJ, Velasquez WS, Link B, Maloney DG, et al. Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. J Clin Oncol. 1999;17:1851-7.
7. Adler MJ, Dimitrov DS. Therapeutic antibodies against cancer. Hematol Oncol Clin North Am. 2012;26:447-81.
8. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140-74.
9. Khouri IF, Saliba RM, Hosing C, Okoroji GJ, Acholonu S, Anderlini P, et al. Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2005;23:2240-7.
10. Neumann F, Harmsen S, Martin S, Kronenwett R, Kondakci M, Aivado M, et al. Rituximab long-term maintenance therapy after autologous stem cell transplantation in patients with B-cell non-Hodgkin's lymphoma. Ann Hematol. 2006;85:530-4.
11. Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, et al. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008;111:5530-6.
12. Robak T. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010;28:1756-65.
13. Vose JM. Antibody-targeted therapy for low-grade lymphoma. Semin Hematol. 1999;36:15-20.
14. Friedberg JW, Neuberg D, Gribben JG, Fisher DC, Canning C, Koval M, et al. Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma. Br J Haematol. 2002;117:828-34.
15. Manches O, Lui G, Chaperot L, Gressin R, Molens JP, Jacob MC, et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood. 2003;101:949-54.
16. + cells by rituximab. Blood. 2003;101:1071-9.
17. Demidem A, Hanna N, Hariharan H, Bonavida B. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. FASEB J. 1995;9:A206.
18. Hofmeister JK, Cooney D, Coggeshall KM. Clustered CD20 induced apoptosis: src-family kinase, the proximal regulator of tyrosine phosphorylation, calcium influx, and caspase 3-dependent apoptosis. Blood Cells Mol Dis. 2000;26:133-43.
19. Pedersen IM, Buhl AM, Klausen P, Geisler CH, Jurlander J. 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. 2002;99:1314-9.
20. Mathas S, Rickers A, Bommert K, Dorken B, Mapara MY. Anti-CD20- and B-cell receptor-mediated apoptosis: evidence for shared intracellular signaling pathways. Cancer Res. 2000;60:7170-6.
21. van der Kolk LE, de Haas M, Grillo-López AJ, Baars JW, van Oers MH. Analysis of CD20-dependent cellular cytotoxicity by G-CSF-stimulated neutrophils. Leukemia. 2002;16:693-9.
22. Polyak MJ, Tailor SH, Deans JP. Identification of a cytoplasmic region of CD20 required for its redistribution to a detergent-insoluble membrane compartment. J Immunol. 1998;161:3242-8.
23. Cragg MS, Morgan SM, Chan HT, Morgan BP, Filatov AV, Johnson PW, French R, Glennie MJ. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood. 2003;101:1045-52.
24. Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: signaling through lipid rafts. Immunology. 2002;107:176-82.
25. Semac I, Palomba C, Kulangara K, Klages N, van Echten-Deckert G, Borisch B. Anti-CD20 therapeutic antibody rituximab modifies the functional organization of rafts/microdomains of B lymphoma cells. Cancer Res. 2003;63:534-40.
26. Bezombes C, Grazide S, Garret C, Fabre C, Quillet-Mary A, Muller S, et al. Rituximab antiproliferative effect in B-lymphoma cells is associated with acid-sphingomyelinase activation in raft microdomains. Blood. 2004;104:1166-73.
27. Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: signaling through lipid rafts. Immunology. 2002;107:176-82.
28. Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B. Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res. 2005;65:264-76.
29. Alas S, Bonavida B. Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin's lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res. 2001;61:5137-44.
30. Vega MI, Huerta-Yepaz S, Garban H, Jazirehi A, Emmanouilides C, Bonavida B. Rituximab inhibits p38 MAPK activity in 2F7 B NHL and decreases IL-10 transcription: pivotal role of p38 MAPK in drug resistance. Oncogene. 2004;23:3530-40.
31. Jazirehi AR, Vega MI, Chatterjee D, Goodglick L, Bonavida B. Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL down-regulation, and chemosensitization of non-Hodgkin's lymphoma B cells by rituximab. Cancer Res. 2004;64:117-26.
32. Suzuki E, Bonavida B. Rituximab inhibits the constitutively activated PI3K-Akt pathway in B-NHL cell lines: involvement in chemosensitization to drug-induced apoptosis. Oncogene. 2007;26:6184-93.
33. Vega MI, Huerta-Yepez S, Martinez-Paniagua M, Martinez-Miguel B, Hernandez-Pando R, González-Bonilla CR, et al. Rituximab-Mediated Cell Signaling and Chemo/Immuno-sensitization of Drug-Resistant B-NHL Is Independent of Its Fc Functions. Clin Cancer Res. 2009;15:6582-94.
34. Alas S, Bonavida B. Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clin Cancer Res. 2003;9:316-26.
35. Jazirehi AR, Gan XH, De Vos S, Emmanouilides C, Bonavida B. Rituximab (anti-CD20) selectively modifies Bcl-xL and apoptosis protease activating factor-1 (Apaf-1) expression and sensitizes human non-Hodgkin's lymphoma B cell lines to paclitaxel-induced apoptosis. Mol Cancer Ther. 2003;2:1183-93.
36. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109:S81-96.
37. Dixit V, Mak TW. NF-κB signaling. Many roads lead to Madrid. Cell. 2002;111:615-9.
38. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489-501.
39. Arancia G, Malorni W, Donelli G. Cellular mechanisms of lymphocyte-mediated lysis of tumor cells. Ann Ist Super Sanita. 1990;26:369-84.
40. Shresta S, Pham CT, Thomas DA, Graubert TA, Ley TJ. How do cytotoxic lymphocytes kill their targets? Curr Opin Immunol. 1998;10:581-7.
41. Wilson NS, Dixit V, Ashkenazi A. Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol. 2009;10:348-55.
42. Vega MI, Jazirehi AR, Huerta-Yepez S, Bonavida B. Rituximab-induced inhibition of YY1 and Bcl-xL expression in Ramos non-Hodgkin's lymphoma cell line via inhibition of NF-kappa B activity: role of YY1 and Bcl-xL in Fas resistance and chemoresistance, respectively. J Immunol. 2005;175:2174-83.
43. Garban HJ, Bonavida B. Nitric oxide inhibits the transcription repressor Yin-Yang 1 binding activity at the silencer region of the Fas promoter: a pivotal role for nitric oxide in the up-regulation of Fas gene expression in human tumor cells. J Immunol. 2001;167:75-81.
44. Huerta S, Baay-Guzman G, Gonzalez-Bonilla CR, Livingston EH, Huerta-Yepez S, Bonavida B. In vitro and in vivo sensitization of SW620 metastatic colon cancer cells to CDDP-induced apoptosis by the nitric oxide donor DETANONOate: involvement of AIF. Nitric Oxide. 2009;20:182-94.
45. Daniel D, Yang B, Lawrence DA, Totpal K, Balter I, Lee WP, et al. Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts. Blood. 2007;110:4037-46.
46. McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti- CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825-33.
47. Davis TA, Grillo-Lopez AJ, White CA, McLaughlin P, Czuczman MS, Link BK, et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000;18:3135-43.
48. Abdollahi S, Chong EA, Olin RL, et al. The impact of rituximab resistance on overall survival rate in low-grade follicular lymphoma. Blood (ASH Annual Meeting Abstracts). 2008;112:3783 [abstract].
49. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2009 (vintage 2009 populations). National Cancer Institute. Bethesda, MD: National Cancer Institute; 2012 (based on the November 2011 SEER data submission, posted to the SEER website April 2012). Available at: http://seer.cancer.gov/csr/1975-2009-pops09/. Accessed June 6, 2012.).
50. Wang M, Han XH, Zhang L, Yang J, Qian JF, Shi YK, et al. Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leukemia. 2008;22:179-85.
51. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99:754-8.
52. Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003;21:3940-7.
53. Macor P, Tripodo C, Zorzet S, Piovan E, Bossi F, Marzari R, et al. In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab. Cancer Res. 2007;67:10556-63.
54. Kennedy GA, Tey SK, Cobcroft R, Marlton P, Cull G, Grimmett K, et al. Incidence and nature of CD20-negative relapses following rituximab therapy in aggressive B-cell non-Hodgkin's lymphoma: a retrospective review. Br J Haematol. 2002;119:412-6.
55. Jazirehi AR, Vega MI, Bonavida B. Development of rituximab-resistant lymphoma clones with altered cell signaling and cross-resistance to chemotherapy. Cancer Res. 2007;67:1270-81.
56. Terui Y, Mishima Y, Sugimura N, Kojima K, Sakurai T, Mishima Y, et al. Identification of CD20 C-terminal deletion mutations associated with loss of CD20 expression in non-Hodgkin's lymphoma. Clin Cancer Res. 2009;15:2523-30.
57. Beum PV, Kennedy AD, Williams ME, Lindorfer MA, Taylor RP. The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes. J Immunol. 2006;176:2600-9.
58. Burger JA, Gandhi V. The lymphatic tissue microenvironments in chronic lymphocytic leukemia: in vitro models and the significance of CD40-CD154 interactions. Blood. 2009;114:2560-1.
59. Colombat P, Watier H. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99:754-8.
60. Golay J, Zaffaroni L, Vaccari T, Lazzari M, Borleri GM, Bernasconi S, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000;95:3900-8.
61. Jazirehi AR, Bonavida B. In: Cree IA, editor. Cancer cell culture: methods and protocols. 2nd ed. New York: Springer; 2011:407-19.
62. Ternant D, Henin E, Cartron G, Tod M, Paintaud G, Girard P. Development of a drug-disease simulation model for rituximab in follicular non-Hodgkin's lymphoma. Br J Clin Pharmacol. 2009;68:561-73.
63. Pederson AE, ungersen MB, Pedersen CD. Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies. Immunology. 2011;133(2):239-45.
64. de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, et al. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009;27:5023-30.
65. Hiraga J, Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood. 2009;14 (113):4885-93.
66. Small GW, McLeod HL, Richards KL. Analysis of innate and acquired resistance to anti-CD20 antibodies in malignant and nonmalignant B cells. Peer J. 2013;1:e31.
67. Czuczman MS, Olejniczak S, Gowda A, Kotowski A, Binder A, Kaur H, Knight J, Starostik P, Deans J, Hernandez-Ilizaliturri FJ. Acquirement of rituximab resistance in lymphoma cell lines is associated with both global CD20 gene and protein down-regulation regulated at the pretranscriptional and posttranscriptional levels. Clin Cancer Res. 2008;14:1561-70.
68. Bram EA, Thudium K, Khubchandani S, Tsai PC, Olejniczak SH, Bhat S, Riaz W, Gu J, Iqbal A, Campagna R, Knight J, Mavis C, Hoskin P, Deeb G, Gibbs JF, Fetterly G, Czuczman MS, Hernandez-Ilizaliturri FJ. Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas. Br J Hematol. 2011;153:599-611.
69. Gu JJ, Hernandez-Illizaliturri FJ, Kaufman GP, Czuczman NM, Mavis C, Skitzki JJ, et al. The novel proteasome inhibitor carfilzomib induces cell cycle arrest, apoptosis and potentiates the anti-tumor activity of chemotherapy in rituximab-resistant lymphoma. Br J Haematol. 2013;162(5):657-69.
70. Gu JJ, Hernandez-Illizaliturri FJ, Mavis C, Czuczman NM, Deeb G, Gibbs J, et al. MLN2238, a proteasome inhibitor, induces caspase-dependent cell death, cell cycle arrest, and potentiates the cytotoxic activity of chemotherapy agents in rituximab-chemotherapy-sensitive or rituximab-chemotherapy-resistant B-cell lymphoma preclinical models. Anticancer Drugs. 2013;24:1030-8.
71. Maiso P, Carvajal-Vergara X, Ocio EM, López-Pérez R, Mateo G, Gutiérrez N, et al. The histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance. Cancer Res. 2006;66:5781-9.
72. Shimizu R, Kikuchi J, Wada T, Ozawa K, Kano Y, Furukawa Y. HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells. Leukemia. 2010;24:1760-8.
73. Wanner K, Hipp S, Oelsner M, Ringshausen I, Bogner C, Peschel C, et al. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitizes DLBCL cells to rituximab. Br J Haematol. 2006;134:475-84.
74. Waters JS, Webb A, Cunningham D, Clarke PA, Raynaud F, di Stefano F, et al. Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J Clin Oncol. 2000;18:1812-23.
75. Pro B, Leber B, Smith M, Fayad L, Romaguera J, Hagemeister F, et al. Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma. Br J Haematol. 2008;143:355-60.
76. van der Kolk LE, Grillo-Lopez AJ, Baars JW, van Oers MH. Treatment of relapsed B-cell non-Hodgkin's lymphoma with a combination of chimeric anti-CD20 monoclonal antibodies (rituximab) and G-CSF: final report on safety and efficacy. Leukemia. 2003;17:1658-64.
77. Khan KD, Emmanouilides C, Benson DM, Jr, Hurst D, Garcia P, Michelson G, et al. A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma. Clin Cancer Res. 2006;12:7046-53.
78. Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, et al. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014;120:222-8.
79. Xuan C, Steward KK, Timmerman JM, Morrison SL. Targeted delivery of interferon-alpha via fusion to anti-CD20 results in potent antitumor activity against B-cell lymphoma. Blood. 2010;115:2864-71.
80. Vega GG, Vega MI, Huerta-Yepez S, Jazirehi A, Mayani H, Martinez-Maza O, Morrison S, Bonavida B. Cytotoxic activity of anti-CD20-hIFN-α on rituximab-resistant B-NHL clones and synergy with chemotherapy. Blood. 2011;118:3499.
81. Hagenbeek A, Fayad L, Delwail V, et al. Evaluation of ofatumumab, a novel human CD20 monoclonal antibody, as single agent therapy in rituximab-refractory follicular lymphoma. Blood. 2010;114:385-6.
82. Lemery SJ, Zhang J, Rothmann MD, Yang J, Earp J, Zhao H, et al. U.S. Food and Drug Administration approval: ofatumumab for the treatment of patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. Clin Cancer Res. 2010;16:4331-8.
83. Czuczman MS, Fayad L, Delwail W, Cartron G, Jacobsen E, Kuliczkowski K, et al. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012;119:3698-704.
84. Salles GA, Morschhauser F, Cartron G, et al. A phase I/II study of RO5072759 (GA101) in patients with relapsed/refractory CD20p malignant disease. Blood. 2008;112:93.
85. Dimitrov DS, Marks JD. Therapeutic antibodies: urrent state and future trends -is a paradigm change coming soon? Meth Mol Biol. 2009;525:1-27.
86. Skerra A. Alternative non-antibody scaffolds for molecular recognition. Curr Opin Biotechnol. 2007;18:295-304.
87. Chen W, Dimitrov DS. Human monoclonal antibodies and engineered antibody domains as HIV-1 entry inhibitors. Curr Opin HIV AIDS. 2009;4:112-7.