The role of OKT3 in clinical transplantation

Abstract

OKT3 is a murine monoclonal anti-T cell antibody that is directed to CD3, a five-chain molecular complex found in association with the T cell receptor for antigen. OKT3 was the first monoclonal antibody to be used in organ transplantation and during the past 10 years there has been extensive experience of its use both for preventing and treating rejection in organ transplantation. OKT3 blocks T cell function by modulating CD3 and the T cell receptor from the T cell surface. A reaction to OKT3 results from cytokines released when OKT3 first reacts with T cells. This reaction is generally mild but can be severe. First rejections following kidney transplantation are reversed in approximately 95% of cases. Steroid-resistant rejections are also susceptible to OKT3 but in only approximately 75% of cases. When used for prophylaxis, OKT3 completely blocks rejection in 95% of patients and significantly delays the onset of rejection in those who do reject. Antibodies to OKT3 are produced in approximately 75% of patients receiving it. However, seldom are the antibodies to OKT3 present in high titer and only in those cases is successful re-use of OKT3 prevented. As is the case with all potent immunosuppressive drugs, the use of OKT3 is associated with increased viral, specifically cytomegalovirus, infections. However, it appears that reduction of concomitant immunosuppression decreases the incidence of severe infections. Unquestionably, OKT3 has been a useful addition to the immunosuppression used for organ transplantation. In addition, its use has stimulated research on other monoclonal antibodies for use in organ transplantation.

Cell-Specific Multifunctional Processing of Heterogeneous Cell Systems in a Single Laser Pulse Treatment

“…We applied two NP types with different PNB generation efficacies, 60 nm hollow gold nanoshells (NS) that generate maximal PNBs and 60 nm solid gold spheres (NSP) that generate much smaller PNBs under identical optical excitation conditions . Both NP types were used in plain and OKT3 antibody-conjugated forms (OKT3 antibody recognizes CD3 receptor expressed in the employed J32 model cells and is also employed in the clinic for manipulation with human T-cells , ). The NS-OKT3-targeted J32 cells (CD3-positive) were labeled with red fluorescent marker (Calcein Red AM), and the NSP-OKT3-targeted J32 cells were labeled with blue fluorescent marker (DAPI) for their identification through fluorescent imaging.…”

“…A PNB is not a particle but a transient nanosecond event, a vapor nanobubble that is generated around a gold nanoparticle (NP) after it absorbs a short laser pulse, converts its energy into heat, and evaporates its liquid environment in a nanoexplosive manner (Figure ). We recently demonstrated that PNBs allow optical detection − and transmembrane injection of molecular cargo − and the immediate destruction (elimination) of specific target cells with high speed and selectivity and without collateral damage even when the majority of the cells are nontarget. ,, The specific function, payload delivery or destruction, is determined by the maximal size of the PNB (Figure ), which, in turn, is determined by the NP’s properties and by the energy of the laser pulse. − We hypothesized that the ability of each NP type to generate PNBs of different sizes under identical optical excitation coupled with the cell-specific targeting and clustering of NPs conjugated to cell-specific antibodies would allow the simultaneous transfer of molecular cargo into gold sphere-targeted cells and the destruction of gold shell-targeted cells in a simultaneous bulk treatment of a heterogeneous cell system with high efficacy, speed, and selectivity and with low toxicity (Figure ). This technology would create a universal platform for cell and gene therapy including stem cell transplantation.…”

Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody

“…CD3 targeting antibodies can be used for different purposes: the muromonab-CD3 antibody was approved to prevent allograft rejection after organ transplantation 34,35 . However, systemic Tcell activation led to side effects with strong cytokine release.…”