Table 1 AlloIgG tumor immunotherapy
From: Perspective view of allogeneic IgG tumor immunotherapy
Ref. | Antibody | Stimuli | Subject | Tumor | Administration | Result (% tumor free, tumor size mm2) | Conclusion |
|---|---|---|---|---|---|---|---|
[5] | AlloIgG-IC+BMDC | No | Mouse/in vitro | B16 melanoma and LMP pancreatic tumor | S.C Tumors removed upon reaching 25–55 mm2, leaving tumor-free margins | % tumor free LMP: 100% B16: > 40d, 75% (n = 5) | Injecting alloIgG-IC+BMDC protected naive mice from tumor challenge |
AlloIgG-IC | Poly(I:C), TNFα+CD40L or IFNγ+D40L | Mouse/in vitro | B16 and LL/2 tumors | Intratumoral injection | Tumor size: AlloIgG-IC+TNFα+CD40L: B16 < 8d 20 → 0 (n = 6); LL/2 < 10d 20 → 0 (n = 8) alloIgG-IC+Poly(I:C): B16 < 8d 20 → 7 (n = 6) | PolyI:C, TNFα+CD40L or IFNγ+CD40L enabled activation of TADC and alloIgG-IC uptake | |
Crosslinked-synIgG-IC+BMDC | No | Mouse/in vitro | B16 | Crosslinked synIgG onto B16 membrane proteins and incubation with BMDC | % tumor free: 80% (n = 8) | Binding of IgG to the tumor cell surface, rather than the origin of the IgG, was critical | |
Anti-GP-NMB | TNFα+CD40L | Mouse/in vitro | B16 | Intratumoral injection | Tumor size (mm2): < 15d 20 → 20 (n = 8) | Anti-GP-NMB+αCD40+TNFα induced significant FcγR-dependent tumor regression | |
AlloIgG-IC | TNFα+CD40L | Mouse/in vitro | Metastases and primary 4T1 breast tumors |  | Tumor number: 0 (n = 4) Primary tumor size: 0 (n = 5) | AlloIgG+αCD40+TNFα led to almost complete resolution of metastases and primary tumors | |
|  | AlloIgG-IC | TNFα+CD40L | Human/in vivo | Malignant pleural mesothelioma |  |  | Drive the proliferation and activation of autologous CD4+ T cells |
[96] | Anti-TRP1 antibody | TNFα+CD40L | Mouse/in vitro | B16F10/ret transgenic mice | Allowed B16F10 to grow until they reached a palpable size. Then, intratumoral injection | Tumor size (mm2): Treated on < 12d or tumor smaller than < 20 mm2: tumor regression > 12d: inert | TNFα+anti-CD40+anti-TRP1 antibody fails to eradicate late-stage melanoma tumors (n = 4) |
[64] | AlloIgG-IC+BMDC | No | Mouse/in vitro | B16F10/LMP | Tumors reached 20–25 mm2 in size then surgically removed, leaving margins of approximately 1 mm | Tumor free: LMP: 100% B16: > 40d, 60% (n = 10 for control group and n = 5 in each treatment) | AlloIgG-IC-loaded BMDC prevent tumor recurrence following resection |
AlloIgG-IC+TADC/MoDC | SHP-1/2 inhibitor + ionomycin | Mouse/in vitro | B16F10 | MoDC&TADC cultured overnight with alloIgG-IC alone or with SHP-1/2 inhibitor + ionomycin, then s.c. injected naive mice. B16 cells challenged on d5 | Tumor free: AlloIgG-IC+MoDC+SHP-1/2inhib + ionomycin:100% AlloIgG-IC+TADC+SHP-1/2inhib + ionomycin: > 15d: 75% (n = 10 control, n = 5 test) | Simultaneous blockade of SHP-1 and phosphatases regulating Akt enables tumor and MoDC activation to facilitate tumor rejection | |
[87] | AlloIgG-IC | IFNγ+CD40L | Mouse/in vitro | MMTV-PyMT triple-neg. breast cancer | Tumors grew to 25 mm2, intratumoral injection | Tumor size (mm2): 25 → 0 | The effective tumor-binding antibody therapy activates dendritic cells, which can prime T cells in the periphery |
[101] | Anti-TRP1 antibody | After 6 days of treatment with anti-TRP1+TNFα+CD40L, CD4+ and CD8+ T cells isolated from the tumors, blood, and DLN | Mouse/in vitro | B16 melanoma | CD4+ or CD8+ T cells with or without anti-TRP1+ with or without DC stimuli injected i.v. into tumor-bearing mice | Tumor size (mm2): Anti-TRP1+TNFα+CD40L+CD4+ T cells: 25 → 20 Anti-TRP1+TNFα+CD40L+CD8+ T cells: 25 → 65 | Adoptive transfer of CD4+ T cells, but not CD8+ T cells, induces potent tumor regression when combined with tumor-binding antibodies |
Anti-TRP1 antibody | TNFα+CD40L+PB or tumor or DLN CD4+ T cells | Mouse/in vitro | B16 melanoma | Anti-TRP1+TNFα+CD40L+PB or tumor or DLN CD4+ T cells injected i.v. into tumor-bearing mice | Tumor size (mm2): TNFα+CD40L+tumor or DLN CD4+ T cells: 25 → 10 TNFα+CD40L+PB CD4+ T cells: 25 → 100 | CD4+ T cells from the tumor and DLN, but not from peripheral blood, directly kill tumor cells coated with IgG antibodies | |
[97] | Anti-TRP1 antibody | TNFα+CD40L | Mouse/in vitro | B16 melanoma |  | Tumors were completely eradicated in all mice. Nonetheless, after approximately 10d, half the mice developed recurrent tumors that were resistant to subsequent treatments | Cell-in-cell formation spatially prevents the penetration of T-cell-derived lytic granules to the inner tumor cells |