Table 3.
Source, production and immunogenicity of IgM antibodies in early phase clinical trials.
| Target Antigen Class | Antibody | Antigen | IgM Source | Production Cell | Indication | Clinical Trial | Dose | Immunogenicity in Humans | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Lipopolysaccharide | E5 | J5 lipid A | Mouse B cells | Hybridoma with mouse myeloma | Sepsis | Phase 1 | 0.1, 0.5, 2, 7.5, 15 mg/kg | 3 of 9 subjects | Harkonen 1988 [129] |
| HA-1A | J5 lipid A | Human B cells | Heteromyeloma with lymphoma spleen cells | Sepsis | Phase 1 | 25, 100, 250 mg | 0 of 34 subjects | Fisher 1990 [130] | |
| MAB-T88 | LPS | Human B cells | Hybridoma with mouse myeloma | Neutropenia | Phase 1 | 1, 4, 8 mg/kg single dose | 0 of 9 subjects | Daifuku 1992 [131] | |
| Mab cocktail (5 IgM) | LPS | Human B cells | Normal adults P. aeruginosa bacteremia | Phase 1 | 0.75 to 3.0 mg/kg | 12 subjects 8 subjects | Saravolatz 1991 [132] | ||
| AR-101 (KBPA-101) | LPS | Human B cells | Hybridoma with mouse myeloma | Nosocomial P. aeruginosa pneumonia | Phase 2a | 1.2 mg/kg × 3 | 0 of 18 subjects | Lu 2011 [133] | |
|
Glycolipid/
Proteolipid |
L612 | Ganglioside GM3 | Human B cells | EBV-transformed patient B cells | Melanoma | Phase 1 | 960, 1440, 1920 mg 48 h infusion | 0 of 9 subjects | Irie 2004 [134] |
| MORAb-028 | Ganglioside GD2 | Human B cells | Hybridoma with human/mouse myeloma | Melanoma | Phase 1 | 1 or 2 mg/cm2/day × 5 days, repeated 2× | 18 subjects | NCT-01123304 [135] | |
| rHIgM22 | CNS myelin proteolipid | Human B cells | Hybridoma with mouse myeloma | Multiple sclerosis/neuronal degeneration diseases | Phase 1 | 0.025 to 2 mg/kgsingle dose | 55 subjects | Eisen 2017 [136] | |
| Glycan | Fanolesomab-Tc99 | CD15 (carbohydrate) | Mouse B cells | Hybridoma with mouse myeloma | Healthy volunteers | Phase 1 | 125 µg × 2 (21 days apart) | 5 of 30 subjects | Line 2004 [137] |
| PAT-SC1 | CD55 (glycan isoform) | Human B cells | Recombinant production Per.C6 cells | Gastric cancer | Phase 1 | 20 mg single dose | 51 subjects | Hensel 2014 [138] | |
| mAb216 | CDIM (carbohydrate) | Human B cells | Heteromyeloma with lymphoma spleen cells | B-lineage ALL | Phase 1 | 1.25 mg/kg to 5 mg/kg 3 + 2 dose escalation | 0 of 13 subjects | Liedtke 2012 [139] | |
| PAT-SM6 | GRP78 (O-linked glycan) | Human B cells | Recombinant production Per.C6 cells | Multiple myeloma | Phase 1 | 0.3, 1 3 or 6 mg/kg 4 doses over 2 weeks | 0 of 12 subjects | Rasche 2015 [140] | |
| Protein | Campath-1M | CD52 | Rat B cells | Hybridoma with rat myeloma | Graft vs. host disease | Phase 2 | 25 mg bid × 10 | (not tested) | Friend 1989 [141] |
| Mab 16.88 | Colon cancer antigen | Human B cells | Hybridoma with mouse myeloma | Colorectal cancer | Phase 1 | 8 mg, then 200, 500 or 1000 mg | 0 of 20 subjects | Haisma 1991 [142] | |
| ABX-CBL | CD147 | Mouse B cells | Hybridoma with mouse myeloma | Graft vs. host disease | Phase 1 | 0.2 to 0.3 mg/kg 9 doses | 0 of 51 subjects | Deeg 2001 [143] | |
| TOL101 | αβ TCR | Mouse B cells | Hybridoma with mouse myeloma | Renal transplant | Phase 2 | 0.3, 1.4, 7, 14, 28, 42 mg 5 daily doses | 1 of 36 subjects | Getts 2014 [144] | |
| ARG098 | FAS | Mouse: Human B cells (chimeric) | Hybridoma with mouse myeloma | Rheumatoid arthritis | Phase 1/2 | up to 10 μg/knee (intraarticular) | 43 subjects | Matsubara 2013 [145] |