Resimmune or A-dmDT390-bisFv(UCHT1) is an experimental drug — an anti-T cell
immunotoxin
An immunotoxin is an artificial protein consisting of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell. They are used for the treatment of some kinds of c ...
— that is being investigated for treatment of blood cancers such as
cutaneous T cell lymphoma
Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B-cell-related), CTCL is caused by a mutation of T cells. The cancerous T ...
(CTCL).
It was developed by Doctors Neville, Woo, and Liu while at the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH) and is under exclusive license to Angimmune, LLC. The therapy has potential applications for lymphomas and T cell driven
autoimmune diseases
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
, including
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
, and
graft-versus-host disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donor's immune system which remain wit ...
following stem cell or bone marrow transplant.
Clinical trials
Since 2009, Resimmune is being tested against cutaneous T cell lymphoma, and is in a Phase II trial: Immunotoxin Therapy for Patients With T-cell Diseases. All patients had failed at least one conventional therapy. In the Phase I portion of the trail, a subgroup of nine patients was identified with an 89% response rate. This subgroup was Stage IB-IIB with mSWAT scores of less than 50. The complete response rate was 50% (two of which are over 72 months duration and could represent cures). A major exclusion to entering the trial is a past history of heart disease, or prior treatment with alemtuzumab (Campath).
A second clinical trial is open to test if Resimmune can act as an immunomodulator of late stage metastatic melanoma.
Description of molecule
Resimmune is a bivalent anti-T cell immunotoxin, . The
diphtheria toxin
Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...
moiety has been modified to include an NH2 terminal alanine (A) and two double mutations (dm) have been made to prevent glycosylation in the eukaryotic expression system, Pichia pastoris (Liu et al., 2000; Thompson et al., 2001; Woo et al., 2002). The bivalent immunotoxin, contains the first 390 amino acid residues of diphtheria toxin (DT) and two tandem sFv molecules derived from UCHT1 parental antibody (an anti-CD3 antibody). The first 390 amino acid residues of DT (DT390) contain the catalytic domain or A chain of DT that inhibits protein synthesis by ADP ribosylation of elongation factor 2 (EF-2) and the translocation domain that translocates the catalytic domain to the cytosol by interaction with cytosolic Hsp90 and thioredoxin reductase (Ratts et al., 2003). This single chain recombinant immunotoxin selectively kills human malignant and transiently depletes normal . Malignant are 30-fold more sensitive to compared to normal resting .
Mechanism of action
Resimmune works by killing malignant , targeting the CD3 T cell receptor complex and transiently depleting all by 2-3 log units. After the four-day treatment, normal are repopulated by homeostatic proliferation. This process may have an
immunomodulatory
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
effect that leads to further elimination of residual tumor cells by activation of novel naïve .
/ref>
References
{{Reflist, 2
External links
Scott & White Healthcare Cancer Research Institute: Clinical Trial , Cutaneous T-Cell Lymphoma
Antineoplastic drugs
Experimental cancer treatments