Review Article

HLA Class Ia and Ib Polyreactive Anti-HLA-E IgG2a Monoclonal Antibodies (TFL-006 and TFL-007) Suppress Anti-HLA IgG Production by CD19+ B Cells and Proliferation of CD4+ T Cells While Upregulating Tregs

Table 4

Comparison of the unique features of the mAbs TFL-006 and TFL-007 with that of IVIg.

Source, nature, and functionsIntravenous immunoglobulin (IVIg)TFL-006 and TFL-007

ManufacturerSeveral pharmaceutical firmsTerasaki Foundation Laboratory
SourcePurified from pooled plasma of 10,000 blood donors from humans in various countriesImmunized in mice with heavy chain of HLA-ER107 [45, 46]
Murine (to be adapted for human use), not humanized
Nature of antibodyHuman, polyclonal IgG with trace level of IgAMurine, ascites purified monoclonal IgG
Subclass of IgG antibodiesIgG1, IgG2a, IgG3, IgG4IgG2a only [45, 46]
PurityContains soluble HLA antigens and other non-IgG proteins, cytokines, and chemokines100% purified protein of IgG2a [45, 46]
Antibody reactivityHLA-A, HLA-B, HLA-Cw, HLA-E, HLA-F, HLA-GHLA-A, HLA-B, HLA-Cw, HLA-E, HLA-F, HLA-G [45, 46]
HLA-DR, HLA-DQA/DQB, HLA-DPA/DPBNone
Fc-receptors: FcγI, FcγII, FcγIII, FcγIV (tested) [98]FcgII (anticipated)
Blood groups A, B, Rh [99101]Not applicable
Escherichia coli bacterial antigens ranging from 94 to 238Not applicable
Antigens by different preparations of IVIg [102]Not applicable
Human albumin [46, 80]Not applicable
Phospholipids [100]Not applicable
StabilizerManyNone
Protein concentrationHighly variable from 2 to 12%Protein concentration can be adjusted to requirement
CD4+ T cell suppressionPHA or cytokine activated T cells [35, 36] by apoptosis [38]PHA-activated T cells [47]
By nonapoptosis (necrosis) [41],
CD8+ T cell proliferationPHA-activated [36]PHA-activated T cells [47]
B cell proliferationInduce differentiation [42]
No effect on proliferation [43]
Anti-HLA antibody suppressionPRA antibody reduction [44]Reduction in the production of anti-HLA-I and anti-HLA-II IgG [48]
Induce antibody secretion [42, 48]
Suppress selected HLA-II antibody production [48]Suppress production of all HLA-II antibodies [48]
Promote selected HLA-II antibody production [48]
Expansion of TregsPromotes upregulation of Tregs [39]Promotes upregulation of Tregs [M. Taniguchi and M. H. Ravindranath, manuscript in preparation] to distinguish β2-microglobulin-associated HC of HLA-Ia from β2-microglobulin-free HC of HLA-Ia coated on Luminex single-antigen beads (One Lamda/Thermofisher Inc) [91, 92]
Special application