Table 2.

Selected cancer antibodies in development and clinical use: effector cell modulation.

Target	Site	Products	Comments
(A) Surface receptors
HER2	Tumor	Trastuzumab [32], pertuzumab [33]	Pertuzumab interferes with HER2 dimerization
EGFR1	Tumor	Cetuximab [35], panitumumab [36]	EGFR1 is expressed especially in gastrointestinal and head and neck tumors and is modulated by heterodimerization with EGFR3
EGFR3 (HER3)	Tumor	Patritumumab [37,38]	–
Glypican 3	Tumor	GC-33 [39]	Glypican3 is highly expressed in hepatocellular cancer
Ganglioside GD2	Tumor	Dinutuximab [40]	GD2 is over expressed in peripheral neuroblastoma [34]
(B) Checkpoint targets
CTLA4	T cell	Ipilimumab [1], tremelimumab [41]	Ipilumumab was the first approved check point agent
PD-1	T cell	Nivolumab [42], pembrolizumab [43] pidilizumab [44]	Nivolumab is approved in melanoma and lung cancer; pembrolizumab is approved for advanced melanoma refractory to ipilumumab, other agents remain in development
PDL-1	APC/tumor	BMS936559 [45], MPDL3280A[46], MEDI- 4736 [47], avelumab [48]	Blocking PDL1 has theoretical advantage of interfering with PD-1 stimulation and also targeting tumor cells for ADCC
KIR	T cell	Lirilumab [49]	–
LAG-3	T cell	BMS 986016 [50]	–
(C) Second signal targets
CD28	T cell	TGN1412 [51,52]	TGN 1412 was the CD-28 agonist that induced severe cytokine storm in Phase I
CD27	T cell	CDX-1127 (varlilumab) [53]	CDX 1127 is being developed for solid and hematologic indications in early-phase studies
CD137(41BB)	T cell	Urelumab [54], PF05082566 [55]	The 41BB agonist urelumab and PF05082566 are lgG4 and lgG2 antibodies, respectively
CD40 [56]	APC	Dacetuzumab, CP870893 [57,58]	CD40 agonists directly stimulate APC and B cells. Their development has been slowed by toxicity issues
CD134 (OX40)	T cell	MEDI-6383 [59]	The Ox40 agonist MEDI-6383 is a T-cell activator in Phase I trials
GITR [60]	T, B, and NK cells	TRX518 [61], MK4166 [62]	GITR agonists deplete Treg and activates T effectors