(trade name Humira™) generated against tumor necrosis factor (TNF) was the first

phage-display-derived MAb approved by the FDA for the treatment of moderate-to-

severe forms of rheumatoid arthritis (Weinblatt et al. 2003). Subsequently, it has also

been approved in various countries for the treatment of polyarticular juvenile idio-

pathic arthritis in children, psoriasis and psoriatic arthritis, pediatric and adult

Crohn’s disease, ulcerative colitis, etc. Belimumab (marketed as Benlysta™)

generated against B lymphocyte stimulator (BLyS) has been approved by the FDA

for the treatment of systemic lupus erythematosus (SLE) (Navarra et al. 2011).

Table 22.4 lists some other therapeutic antibodies that have been obtained by

using phage-display technology and approved by the US FDA.

22.4.3 Single-B Cell Polymerase Chain Reaction-Derived Therapeutic

Human Antibodies

Rapid development of immunotherapies for newly emerging pathogens such as

influenza virus, Ebola virus, and lately COVID-19, or analysis of antibody

repertoires, depends on highly sophisticated technology platforms such as single-B

cell sorting. In acute cases, it is important to utilize the most rapid direct method for

the isolation of potent human antibodies to generate therapeutic molecules for

clinical applications—even within a few weeks. Immunological response against a

pathogen is enforced by the cellular (CD4 and CD8 T cells) and humoral (B cells)

immune components. Antibody-secreting cells (ASCs) and memory B cells (MBCs)

constitute the primary cellular components of T cell-dependent antibody response to

a variety of viral pathogens. Upon re-exposure to virus, activated MBCs rapidly

differentiate into ASCs that produce high-affinity antibodies and in the steady state

Table 22.4 Partial list of therapeutic human MAbs produced by using phage-display technology

Product

Trade name

Indication

Target

Company

(FDA

approval)

Adalimumab

Humira™

Rheumatoid arthritis

Tumor necrosis factor

(TNF)

Abbott

(2002)

Ranibizumab

Lucentis™

Macular

degeneration

Vascular endothelial

growth factor A

(VEGFA)

Genentech

(2006)

Belimumab

Benlysta™

Systemic lupus

erythematosus (SLE)

B lymphocyte

stimulator (BLyS)

GSK

(2011)

Raxibacumab

Abthrax™

Anthrax

Protective antigen (PA)

GSK

(2012)

Ramucirumab

Cyramza™

Gastric, colorectal,

and non-small cell

lung cancers

Vascular endothelial

growth factor receptor

2 (VEGFR2)

ImClone/

Lilly

(2014)

Necitumumab

Portrazza™

Squamous non-small

cell lung cancer

Epidermal growth

factor receptor (EGFR)

ImClone/

Lilly

(2015)

410

S. K. Gupta and P. Chaudhary