Comparison of various radioactive payloads for a human monoclonal antibody to glycoprotein 41 for elimination of HIV-infected cells.

Background: cART has significantly improved the life expectancy of people living with HIV (PLWH). However, it fails to eliminate the long-lived reservoir of latent HIV-infected cells. Radioimmunotherapy (RIT) relies on antigen-specific monoclonal antibodies (mAbs) for targeted delivery of lethal doses of ionizing radiation to cells. Previously, we have demonstrated that human mAb 2556 against HIV gp41 conjugated with ²¹³ Bismuth radioisotope (t _1/2  = 46 min, alpha-emitter) selectively killed HIV-infected cells. ²²⁵ Actinium (t _1/2  = 9.92 d, alpha-emitter) and ¹⁷⁷ Lutetium (t _1/2  = 6.7 d, beta-emitter) are two long-lived clinically proven radioisotopes for cancer treatment which might be more effective in killing infected cells systemically and in CNS.
Methods: In this study we have conjugated 2556 mAb with ²¹³ Bi, ²²⁵ Ac and ¹⁷⁷ Lu, and compared their ability to kill HIV-infected human peripheral blood mononuclear cells (PBMCs) and monocytes. PBMCs and monocytes from healthy donors were infected with HIV _p49.5 and treated in vitro with increasing concentrations of ²¹³ Bi (4-20 μCi)-, ²²⁵ Ac (20-100 nCi)- and ¹⁷⁷ Lu (4-50 μCi)-2556 mAb.
Results: After three days post-treatment of infected PBMCs and monocytes, ²¹³ Bi- and ¹⁷⁷ Lu-conjugated 2556 mAb reduced virus production measured by p24 level in a dose-dependent manner, whereas, ²²⁵ Ac-2556 showed minimal effect. However, seven days post-treatment all three radioisotopes showed significantly more pronounced reduction of virus replication as compared to control labeled mAb with ²²⁵ Ac-2556 showing the least non-specific killing.
Conclusion: These results indicate that RIT holds promise as a novel treatment option for the eradication of HIV-infected cells that merits further study in combination with cART and reactivation drugs.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
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