Moreover, it signals with high constitutive activity [29, 30] and undergoes constitutive ligand-independent receptor internalization , a feature well suited for immunotoxin
Lee, "Effect of antigen shedding on targeted delivery of immunotoxins
in solid tumors from a mathematical model," PLoS ONE, vol.
Finally, the resulted immunotoxin
with His-tag was purified through immobilized metal ion affinity chromatography (IMAC) using Ni-NTA purification resin and was verified by SDS-PAGE.
One of the biggest challenges for immunotoxin
therapy is its potential immunogenicity, which can originate from either antibody part or toxin part.[sup] To avoid the generation of host anti-murine antibodies against the antibody part of an immunotoxin
, this part can be further humanized or replaced by a fully human counterpart.[sup] As for the more immunogenic toxin domain, it can be reengineered by combining mutations that decrease lymphocyte epitopes to significantly minimize the immunogenicity induced by a foreign toxin protein.[sup] Immunotoxins
with mutations at both B- and T-cell epitopes can theoretically eliminate the issue of immunogenicity.
The left eye of each animal was intravitreally injected with different doses of immunotoxin
melanopsin-SAP (2 [micro]l/eye) (Advanced Targeting Systems, San Diego, CA, USA), consisting of saporin conjugated to a melanopsin polyclonal antibody.
therapy of cancer," Nature Reviews Cancer, vol.
(2001) Lowering the isoelectric point of the Fv portion of recombinant immunotoxins
leads to decreased nonspecific animal toxicity without affecting antitumor activity.
The scientists found that, compared to antiretrovirals alone, the addition of the immunotoxin
significantly reduced both the number of HIV-infected cells producing the virus in multiple organs and the level of HIV in the blood.
Moreover, lintuzumab conjugated with immunotoxin
recombinant gelonin (HUM-195/rGEL) has been under investigation in patients with relapsed/refractory myeloid leukemias .
Karande, "Abrin immunotoxin
: targeted cytotoxicity and intracellular trafficking pathway," PloS ONE, vol.
Using saporin-conjugated antidopamine hydroxylase (DSAP), a selective immunotoxin
that destroys NE and epinephrine (E) containing neurons, loss of NE/E input in the arcuate nucleus resulted in an increase in baseline levels of neuropeptide Y/agouti-related peptide (NPY/AgRP) mRNA expression.
Additionally, multiple INDs are expected in the next 12-24 months resulting from preclinical and discovery work underway to advance multiple antibody, immunotoxin
, and protein decoy candidates, systemic delivery and a next generation RheoSwitch Therapeutic System(R).