An Effective Immuno-PET Imaging Method to Monitor CD8-Dependent Responses to Immunotherapy.

The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity of noninvasive and quantitative technologies capable of monitoring the presence and abundance of CD8(+) T cells and other immune cell subsets. In this study, we describe the generation of (89)Zr-desferrioxamine-labeled anti-CD8 cys-diabody ((89)Zr-malDFO-169 cDb) for noninvasive immuno-PET tracking of endogenous CD8(+) T cells. We demonstrate that anti-CD8 immuno-PET is a sensitive tool for detecting changes in systemic and tumor-infiltrating CD8 expression in preclinical syngeneic tumor immunotherapy models including antigen-specific adoptive T-cell transfer, agonistic antibody therapy (anti-CD137/4-1BB), and checkpoint blockade antibody therapy (anti-PD-L1). The ability of anti-CD8 immuno-PET to provide whole body information regarding therapy-induced alterations of this dynamic T-cell population provides new opportunities to evaluate antitumor immune responses of immunotherapies currently being evaluated in the clinic.

Successful desensitization of a case with desferrioxamine hypersensitivity.

Thalassaemia major is a severe chronic hemolytic disease, resulted with iron overload mainly due to regular blood transfusions. Iron overload may lead to serious organ toxicity and even fatal complications, if no iron excretion is achieved by a chelating agent. First introduced in 1976 as s.c. treatment for thalassaemia major, desferrioxamine (DFO) has substantially improved the life expectancy in the disease. While DFO can cause local allergic reactions including redness, itching, pain and lumps, on rare occasion anaphylactic reactions can occur. The mechanism of anaphylaxis like reactions is not well understood. In this case report, we presented a 10 years-old girl with thalassaemia major who had to stop DFO therapy after appearing of systemic allergic reactions with hypotension, tachycardia, pruritus and urticaria against this drug. Serum IgE level was normal, specific IgE and skin prick tests were negative. Intradermal test was resulted with positive reaction to DFO. The patient was hospitalized and desensitization protocol was initiated with rapid s.c. infusions per 15 min. The protocol was stopped at the 17th cycle because of local reaction reappeared. After that, DFO was further diluted and was restarted with lower dosage and longer infusion period. Then, DFO dosage was increased and the dilutions and infusion times were decreased gradually. By this desensitization programme, the patient would continue to use DFO chelation safely for 10 months.

Immune function in patients with beta thalassaemia receiving the orally active iron-chelating agent deferiprone.

Short-term deferiprone may reduce body iron in some patients with thalassaemia major. Concerns regarding potential immunosuppressive effects of deferiprone have been raised from results of animal studies and case reports in humans. We studied immune function in 57 thalassaemia patients: 36 treated with deferiprone (L1; CP020) and 21 treated with desferrioxamine (DFO). Circulating B lymphocytes were increased in all patient groups. No differences were detected between treatment groups in percentages of circulating lymphocytes, concentrations of IgG, IgM or IgA, specific antibody titres, complement levels, or in vitro lymphocyte proliferation. No clinically important infections were observed in any patient. These data suggest that no clinical or laboratory changes consistent with immuno-suppression or immunodeficiency are observed during deferiprone therapy.

Targeting of macromolecular carriers and liposomes by antibodies to myosin heavy chain.

Macromolecular carriers and liposomes were covalently coupled to monoclonal antibodies against cardiac myosin heavy chain. Deferoxamine-modified polymers bound tightly with 67Ga and 68Ga radioisotopes. Ternary deferoxamine-polylysine antibody conjugates specifically targeted the radioisotopes to a myosin-coated microplate. Scatchard analysis revealed a high affinity of the conjugate for the target with a Kas of approximately 10(8) M-1. Liposomes that contained immobilized antimyosin antibodies were targeted specifically to the myosin-coated plate. Additional coating of these liposomes with polyethylene glycol reduced specific binding to the target in vitro. However, because of the presence of polyethylene glycol on the surface of liposomes, these liposomes had a long half-life and slowly cleared from the blood-stream after intravenous injection. These immunoliposomes showed up to 16- to 18-fold specific localization to the necrotic areas of the myocardium in rabbits with experimental infarction.