Emerging trends and new developments in monoclonal antibodies: A scientometric analysis (1980–2016)

Figures & data

Figure 1. The landscape of mAb (a document co-citation network).

Table 1. Top 10 largest clusters of panorama (time sorting).

Cluster ID	Size	Silhouette	Mean (year)	Label (LLR)
#8	46	0.974	1979	human glioma xenograft model
#6	52	0.975	1980	mouse monoclonal-antibodies
#1	83	0.886	1984	reshaping human-antibodies
#7	52	0.903	1987	phase-I trial
#2	82	0.892	1989	cyto-toxic t-cell
#3	67	0.816	1992	single chain fv
#9	45	0.992	1999	crohns disease
#4	66	0.917	2000	endothelial growth factor
#5	59	0.897	2006	bispecific antibody
#0	98	0.96	2010	antibody drug conjugate

Table 2. References with the strongest citation bursts every year.

	Citation burst
Cited references	Strength	Begin	End	Citation (WOS)	Summary
Herlyn DM (1980)^46	4.6086	1982	1991	263	The study of murine mAb provided an possibilities approach to the treatment of anti-colorectal carcinoma antibodies in humans with immunotherapeutic, but the ADCC had not been discussed whether there will be in humans.
Milstein C (1983)^47	21.9359	1984	1999	371	The utility of hybrid hybridomas in immunohistochemistry and advance the mAb development.
Staerz UD (1985)^48	27.4799	1986	1997	355	Hybrid antibody is the key mechanism of monoclonal antibodies against the T-cell receptor.
Lanzavecchia A (1987)^49	29.6084	1987	1996	208	This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen.
Brennan M (1985)^50	19.222	1988	1997	158	This study describes the preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin G1 fragments.
Laemmli UK (1970)^51	56.923	1989	1997	237,672	The application of bacteriophage.
Lobuglio AF (1989)^52	54.8754	1990	1998	519	Chimeric mAbs were better than murine mAb in clinical trial efficacy of kinetics and immune response.
Nitta T (1990)^53	31.1392	1991	1998	225	This study describes the preliminary trial of specific targeting therapy against malignant glioma.
Ziegler EJ (1991)^54	31.8062	1992	2000	1,212	The efficacy of human mAb was very good in treating gram-negative and septic shock.
Bird RE (1988)^55	22.4002	1993	2000	1,134	This study describes single-chain antigen-binding proteins was used to improve the application of mAb and experted to be better.
Bolhuis RL (1992)^56	23.4994	1994	2000	108	This study describes a bispecific mAb was used for the treatment of ovarian cancer.
Riethmuller G (1994)^57	30.9766	1995	2001	574	Adjuvant therapy with mAb reduces mortality and prolongs remission in patients with colorectal cancer.
Winter G (1994)^58	26.713	1996	2003	1,105	This study describes the application of phage display technology in making antibodies.
Targan SR (1997)^59	50.3401	1998	2007	223	This study describes the application of chimeric mAb cA2 for the short-treatment of crohn's diseaseto by targeting tumor necrosis factor α was effective.
Present DH (1999)^60	43.196	1999	2006	1,588	The chimeric mAb infliximab with the therapeutic target TNFα is effective for the treatment of Crohn's disease.
Mclaughlin P (1998)^61	47.9737	2000	2010	1,864	This study describes rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma.
Rutgeerts P (1999)^62	30.7928	2001	2006	777	This study describes the efficacy and safety of anti–tumor necrosis factor antibody (infliximab) being used in treating crohn's disease.
Clynes RA (2000)^63	29.5272	2002	2012	1,613	This study describes the mechanism of inhibitory Fc receptors were used to against tumor targets by modulating in vivo cytoxicity.
Hanauer SB (2002)^30	34.8937	2003	2012	2,126	The chimeric mAb infliximab with the therapeutic target TNFα is effective for the treatment of Crohn's disease.
Baert F (2003)^64	28.7392	2004	2012	1,115	The chimeric mAb infliximab with the therapeutic target TNFα in the treatment of Crohn's disease can increase risk of infusion reactions and reduce duration of response to treatment.
Hurwitz H(2004)^37	38.9387	2005	2012	6,048	The humanized mAb bevacizumab with the therapeutic target VEGF to fluorouracil-based combination chemotherapy is effective to patients with metastatic colorectal cancer.
Holliger P (2005)^65	33.1524	2007	2016	864	The emerging of engineered antibody fragments and single-domain antibodies in the development of mAb.
Zeidler R (1999)^66	17.716	2008	2012	130	The study describes a new class of intact bispecific antibody was effective to kill tumor cell with the simultaneous activation of T cells and accessory cells.
Phillips GDL (2008)^67	40.1062	2010	2016	401	The study describes the ADC trastuzumab-DM1 targeting HER2-positive breast cancer.
Younes A (2010)^68	34.9501	2011	2016	472	The study describes the ADC brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas.
Doronina SO (2003)^69	36.2901	2012	2016	410	This study describes the development of potent monoclonal antibody auristatin conjugates for cancer therapy.
Junutula JR (2008)^70	59.4501	2013	2016	379	This study describes the therapeutic index can be improved by the site-specific conjugation of a cytotoxic drug to an antibody.
Strop P (2013)^71	29.8272	2014	2016	118	This study describes that ADC stability and pharmacokinetics can be significant impacted by the conjugation site in a species-dependent manner.

Table 3. The summary of the top 5 largest clusters.

Cluster	Size	University	Enterprise	Research institute	Hospital
#0	44	70.45%	13.64%	9.09%	6.82%
#1	36	63.89%	19.44%	11.11%	5.56%
#2	35	45.71%	22.86%	25.71%	5.71%
#3	25	48.00%	16.00%	32.00%	4.00%
#4	18	61.11%	11.11%	27.78%	0.00%

Figure 2. Top published institutions.

Table 4. Top 20 cited journals.

Cited frequency	Centrality	Year	Cited journal
5025	0.54	1981	Proc Natl Acad Sci USA
4475	0.46	1982	Cancer Res
4012	0.32	1981	J Immunol
3817	0.09	1982	New Eng J Med
3782	0.1	1982	Nature
3461	0.07	1982	Science
3159	0.19	1985	J Biol CHem
3084	0.08	1982	Blood
2891	0.15	1986	J Clin Oncol
2631	0.05	1998	Clin CANCER RES
2588	0.1	1981	Lancet
2312	0.04	1981	J Exp Med
2300	0.04	1981	Int J Cancer
2123	0.04	1985	J Immunol Methods
1955	0.1	1981	J Clin Invest
1662	0.01	1982	Brit J Cancer
1617	0.23	1998	Nat Biotechnol
1608	0.02	1986	Cell
1574	0	1998	Nat Med
1440	0.03	1981	Cancer

Table 5. The search strategies used in the database.

Dataset	Types	Search strategies
DA	murine mAbs	TS=((“mouse antibody” or “murine antibody” or “mouse antibodies” or “murine antibodies” or “mouse monoclonal antibody” or “murine monoclonal antibody” or “mouse monoclonal antibodies” or “murine monoclonal antibodies”) and (“therapeutic” or “immunotherapeutic” or “clinical” or “clinic” or “therapy” or “therapies” or “therapeutics” or “immunotherapy” or “treatment” or “immunotherapeutics”)) AND Type=(article) AND Language=(English)
DB	chimeric mouse-human antibodies	TS=((“chimeric human mouse antibody” or “chimeric human mouse antibodies” or “chimeric mouse human antibody” or “chimeric mouse human antibodies” or “chimeric antibody” or “chimeric antibodies” or “chimeric monoclonal antibody” or “chimeric monoclonal antibodies”) and (“therapeutic” or “immunotherapeutic” or “clinical” or “clinic” or “therapy” or “therapies” or “therapeutics” or “immunotherapy” or “treatment” or “immunotherapeutics”)) AND Type=(article) AND Language=(English)
DC	humanized mAbs	TS=((“humanized antibody” or “humanized antibodies” or “humanized monoclonal antibody” or “humanized monoclonal antibodies”) and (“therapeutic” or “immunotherapeutic” or “clinical” or “clinic” or “therapy” or “therapies” or “therapeutics” or “immunotherapy” or “treatment” or “immunotherapeutics”)) AND Type=(article) AND Language=(English)
DD	human mAbs	TS=((“human antibody” or “human antibodies” or “human monoclonal antibody” or “human monoclonal antibodies”) and (“therapeutic” or “immunotherapeutic” or “clinical” or “clinic” or “therapy” or “therapies” or “therapeutics” or “immunotherapy” or “treatment” or “immunotherapeutics”) not (polyclonal or serum)) AND Type=(article) AND Language=(English)
DE	bispecific	TS=(“bispecific antibody” or “bispecific antibodies” or “bispecific monoclonal antibody” or “bispecific monoclonal antibodies”) AND Type=(article) AND Language=(English)
DF	antibody drug conjugate	TS=(“antibody drug conjugate” or “antibody drug conjugates”) AND Type=(article) AND Language=(English)

Table 6. A summary of the data sets collected.

Dataset	Collection	Duration	Results	References	Keywords	Authors	Institutions
DA	TS	1980–2016	2,507	62,703	10,737	14,127	1,917
DB	TS	1980–2016	1,278	29,310	5,164	7,250	1,018
DC	TS	1980–2016	1,689	45,804	7,275	10,314	1,285
DD	TS	1980–2016	2,376	64,099	9,801	14,663	1,700
DE	TS	1980–2016	1,726	36,840	5,904	7,332	1,667
DF	TS	1980–2016	874	30,684	2,473	3,038	959
DABCDEF	Combined	1980–2016	9,827	202,274	26,500	44,929	7,757

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