Search

IN the late 1980s, Linda A. Rosa, a registered nurse working in Denver, Colorado, was deluged with brochures promoting courses for nurses in crystal healing, color therapy, and a technique [...]

This essay addresses the conundrum of how therapeutic touch despite its lack of effect gained a major foothold in the nursing profession. In this phenomenon, there are several antecedent tensions. One is between doctors and nurses both performing medicine and experiencing that the knowledge and skills of doctors are more highly valued and rewarded than the knowledge and skills of nurses. Another tension is over the knowledge base. Therapeutic touch practitioners describe its roots as humanist contrasting it with doctoring which is based on science. From this base, it seems to have been a small step to an anti-science stance. Critiques from postmodernism, especially critiques of science have been used to frame and bolster the rationale for therapeutic touch.

B7-H3 (CD276), a member of the B7-family of immune checkpoint proteins, has been shown to have immunological and non-immunological effects promoting tumorigenesis [1, 2] and expression correlates with poor prognosis for many solid tumors, including cervical, ovarian and breast cancers [3-6]. We recently identified a tumor-cell autochthonous tumorigenic role for dimerization of the 4Ig isoform of B7-H3 (4Ig-B7-H3) [7], where 4Ig-B7-H3 dimerization in cis activated tumor-intrinsic cellular proliferation and tumorigenesis pathways, providing a novel opportunity for therapeutic intervention. Herein, a live cell split-luciferase complementation strategy was used to visualize 4Ig-B7-H3 homodimerization in a high-throughput small molecule screen (HTS) to identify modulators of this protein-protein interaction (PPI). Notably, the HTS identified several compounds that converged on lipid metabolism (including HMG-CoA reductase inhibitors, also known as statins) as significant inhibitors of 4Ig-B7-H3 dimerization (p < 0.01). In vitro and in vivo murine studies provided evidence that statin-mediated disruption of 4Ig-B7-H3 dimerization was associated with anti-tumor effects. Statin-mediated anti-cancer efficacy was selective for B7-H3-expressing tumors and retrospective analysis of clinical tumor specimens supported the hypothesis that concurrent statin use enhanced clinical outcomes for patients in a B7-H3 restricted manner. Thus, disruption of 4Ig-B7-H3 dimerization provides an unanticipated molecular mechanism linking statin use in cancer therapy and prevention with immune checkpoint., Competing Interests: Competing Interest Statement: The authors declare no competing interests. The University of Texas MD Anderson Cancer Center has filed a patent application on an anti-B7-H3 antibody used in this report (S.T.G., and D.P.W., inventors). The technology is licensed in part to Radiopharm Ventures, LLC. The remaining authors have no conflicts of interest.

Programmed death ligand 1 (PD-L1) is a type 1 transmembrane immunosuppressive protein that is expressed on a wide range of cell types, including cancer cells. Anti-PD-L1 antibodies have revolutionized cancer therapy and have led to improved outcomes for subsets of cancer patients, including triple-negative breast cancer (TNBC) patients. As a result, PET imaging of PD-L1 protein expression in cancer patients has been explored for noninvasive detection of PD-L1 expressing tumors as well as monitoring response to anti-PD-L1 immune checkpoint therapy. Previous studies have indicated that the in vivo stability and in vivo target detection of antibody-based radio-conjugates can be dramatically affected by the chelator used. These reports demonstrated that the chelator HOPO diminishes 89 Zr de-chelation compared to DFO. Herein, we report an improved HOPO synthesis and evaluated a series of novel analogues for thermal stability, serum stability, PD-L1-specific binding using the BT-549 TNBC cell line, PET imaging in vivo , as well as biodistribution of 89 Zr-labeled anti-PD-L1 antibodies in BT-549 xenograft murine models. A new chelator, C5HOPO, demonstrated high stability in vitro and afforded effective PD-L1 targeting in vivo via immuno-PET. These results demonstrated that an improved HOPO chelator is an effective chelating agent that can be utilized to image therapeutically relevant targets in vivo ., Competing Interests: The authors declare the following competing financial interest(s): C.-W.L and M.-C.H. are listed inventors on patent applications for the antibodies contained herein. The remaining authors declare no conflicts of interest., (© 2023 The Authors. Published by American Chemical Society.)