A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl

An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity that Reverses Carfentanil-Induced Respiratory Depression

“…Additionally, some high-affinity drugs have functional groups branching from the center N that may clash with CDR H2 in the bound C10-S66K structure, but the binding observed in Table 1 suggests that CDR H2 should be able to adopt different conformations to accommodate them (Supplemental Figure S2). In contrast, other published antibodies like HY6-F9 24 , FenAb609 12 , and FenAb208 12 have binding pockets that interact with unique functional groups of fentanyl, making them unlikely to bind to fentanyl analogs. Therefore, C10-S66K represents a promising candidate for antibody therapeutics that recognize fentanyl, carfentanil, and related drugs that share the core phenylethyl and piperidinyl group.…”

“…10 Murine and chimeric mAbs have been described previously against members of the opioid family including morphine, heroin, heroin's metabolite 6-acetylmorphine and fentanyl. [11][12][13][14][15] However, from a therapeutic standpoint, the presence of non-human derived antibody regions is a liability often triggering an adverse immune response. Therefore, we began a research program centered on carfentanil with the goal of generating fully human antibodies that can be used to treat drug overdose and that are cross-reactive with the prevalent fentanyl and its analogs.…”

An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression

“…Additionally, some high-affinity drugs have functional groups branching from the center N that may clash with CDR H2 in the bound C10-S66K structure, but the binding observed in Table 1 suggests that CDR H2 should be able to adopt different conformations to accommodate them (Figure 4). In contrast, other published antibodies like HY6-F9, 24 FenAb609, 12 and FenAb208 12 have binding pockets that interact with unique functional groups of fentanyl, making them unlikely to bind to fentanyl analogs. Therefore, C10-S66K represents a promising candidate for antibody therapeutics that recognize fentanyl, carfentanil, and related drugs that share the core phenylethyl and piperidinyl group.…”

“…Murine and chimeric mAbs have been described previously against members of the opioid family including morphine, heroin, heroin’s metabolite 6-acetylmorphine, and fentanyl. − However, from a therapeutic standpoint, the presence of non-human derived antibody regions is a liability often triggering an adverse immune response. Therefore, we began a research program centered on carfentanil with the goal of generating fully human antibodies that can be used to treat drug overdose and that are cross-reactive with the prevalent fentanyl and its analogs.…”