Table 2.

Comparison of SS1P and the Redesigned Anti-Mesothelin Immunotoxin RG7787

	SS1P	RG7787
Targeting moeity	Anti-MSLN dsFv	Humanized anti-MSLN Fab
PE payload	PE containing Domains II and III (PE38)	PE with most of Domain II deleted and Domain III bearing 7 point mutations to remove B cell epitopes (PE24)
Payload size	38-kDa	24-kDa
Full molecule size	62-kDa	72-kDa
Activity in vitro	Picomolar range for many tumor cell lines	Picomolar range for many tumor cell lines
Mouse MTD	0.4 mg/kg I.V. every other day x3*	3.75 mg/kg I.V. every other day x3*
Efficacy in mouse tumor models	Shrinks A431 epidermoid cancer cells expressing transfected mesothelin and complete regressions with chemotherapy (9). Ineffective against KLM1 pancreatic.*	Decreases tumor volume of mesothelin-positive breast (HCC70), gastric (MKN28), and large lung tumors (H596). Cytostatic in KLM1 pancreatic as single agent, but complete regressions with taxane (10, 11, 19)
Immunogenicity	90% of patients make neutralizing anti-drug antibodies after 1 cycle (20, 21)	Limited reactivity to anti-drug antibodies from sera of patients previously treated with SS1P (18)
Current clinical testing	Phase II in combination studies with pentostatin and cyclophosphamide (NCT01362790)	Phase I for mesothelin-positive tumors (NCT02317419)

^*unpublished

MSLN, mesothelin; MTD, maximum tolerated dose