Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy.

Several cancer immunotherapy approaches, such as immune checkpoint blockade and adoptive T-cell therapy, boost T-cell activity against the tumor, but these strategies are not effective in the absence of T cells specific for displayed tumor antigens. Here we outline an immunotherapy in which endogenous T cells specific for a noncancer antigen are retargeted to attack tumors. The approach relies on the use of antibody-peptide epitope conjugates (APECs) to deliver suitable antigens to the tumor surface for presention by HLA-I. To retarget cytomegalovirus (CMV)-specific CD8+ T cells against tumors, we used APECs containing CMV-derived epitopes conjugated to tumor-targeting antibodies via metalloprotease-sensitive linkers. These APECs redirect pre-existing CMV immunity against tumor cells in vitro and in mouse cancer models. In vitro, APECs activated specifically CMV-reactive effector T cells whereas a bispecific T-cell engager activated both effector and regulatory T cells. Our approach may provide an effective alternative in cancers that are not amenable to checkpoint inhibitors or other immunotherapies.

Interprofessional education increases knowledge, promotes team building, and changes practice in the care of Parkinson's disease.

OBJECTIVE: Examine outcomes for the National Parkinson Foundation (NPF) Allied Team Training for Parkinson (ATTP), an interprofessional education (IPE) program in Parkinson's disease (PD) and team-based care for medicine, nursing, occupational, physical and music therapies, physician assistant, social work and speech-language pathology disciplines. BACKGROUND: Healthcare professionals need education in evidence-based PD practices and working effectively in teams. Few evidence-based models of IPE in PD exist. METHODS: Knowledge about PD, team-based care, the role of other disciplines and attitudes towards healthcare teams were measured before and after a protocol-driven training program. Knowledge, attitudes and practice changes were again measured at 6-month post-training. Trainee results were compared to results of controls. RESULTS: Twenty-six NPF-ATTP trainings were held across the U.S. (2003-2013). Compared to control participants (n = 100), trainees (n = 1468) showed statistically significant posttest improvement in all major outcomes, including self-perceived (p < 0.001) and objective knowledge (p < 0.001), Understanding Role of Other Disciplines (p < 0.001), Attitudes Toward Health Care Teams Scale (p < 0.001), and the Attitudes Toward Value of Teams (p < 0.001) subscale. Despite some decline, significant improvements were largely sustained at six-month post-training. Qualitative analyses confirmed post-training practice changes. CONCLUSIONS: The NPF-ATTP model IPE program showed sustained positive gains in knowledge of PD, team strategies and role of other disciplines, team attitudes, and important practice improvements. Further research should examine longer-term outcomes, objectively measure practice changes and mediators, and determine impact on patient outcomes.