Strategies for Improving CAR T Cell Persistence in Solid Tumors.

CAR T cells require optimization to be effective in patients with solid tumors. There are many barriers affecting their ability to succeed. One barrier is persistence, as to achieve an optimal antitumor response, infused CAR T cells must engraft and persist.

Distinct host preconditioning regimens differentially impact the antitumor potency of adoptively transferred Th17 cells.

Background: How distinct methods of host preconditioning impact the efficacy of adoptively transferred antitumor T helper cells is unknown.

Methods: CD4 T cells with a transgenic T-cell receptor that recognize tyrosinase-related peptide (TRP)-1 melanoma antigen were polarized to the T helper 17 (Th17) phenotype and then transferred into melanoma-bearing mice preconditioned with either total body irradiation or chemotherapy.

Results: We found that preconditioning mice with a non-myeloablative dose of total body irradiation (TBI of 5 Gy) was more effective than using an equivalently dosed non-myeloablative chemotherapy (cyclophosphamide (CTX) of 200 mg/kg) at augmenting therapeutic activity of antitumor TRP-1 Th17 cells.

IL15 and IL21: Better When Membrane-Tethered Together on Antitumor T Cells.

Systemic administration of homeostatic γ-chain cytokines mediates antitumor responses in some patients treated with adoptive immunotherapy. Yet many patients experience toxic side effects. New work presented herein suggests these limitations can be overcome by membrane-tethering IL15 and IL21 to T-cell products.

Distinct host preconditioning regimens differentially impact the antitumor potency of adoptively transferred Th17 cells.

Background: Mechanisms by which distinct methods of host preconditioning impact the efficacy of adoptively transferred antitumor T helper cells is unknown.

Methods: CD4 T cells with a transgenic TCR that recognize TRP-1 melanoma antigen were polarized to the T helper 17 (Th17) phenotype and then transferred into melanoma-bearing mice preconditioned with either total body irradiation or chemotherapy.

Results: We found that preconditioning mice with a non-myeloablative dose of total body irradiation (TBI of 5 Gy) was more effective than using an equivalently dosed non-myeloablative chemotherapy (CTX at 200 mg/kg) at augmenting therapeutic activity of anti-tumor TRP-1 Th17 cells.

Longitudinal associations between moral injury perceptions and mental health among healthcare workers during the pandemic.

Objective: The COVID-19 pandemic strained the healthcare system and resulted in higher rates of potentially morally injurious events. These events are perceived as violating one's own moral code, so a more precise construct label could be moral injury perceptions (MIPs). MIPs may exacerbate stress-related symptoms.

Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity.

Unlabelled: Generating stem-like memory T cells (TSCM) is a potential strategy to improve adoptive immunotherapy. Elucidating optimal ways to modulate signaling pathways that enrich TSCM properties could identify approaches to achieve this goal. We discovered herein that blocking the PI3Kδ pathway pharmaceutically to varying degrees can generate T cells with increasingly heightened stemness properties, based on the progressive enrichment of the transcription factors Tcf1 and Lef1.

The yes-associated protein (YAP) is associated with resistance to anti-GD2 immunotherapy in neuroblastoma through downregulation of .

Pediatric patients with high-risk neuroblastoma often relapse with chemotherapy-resistant, incurable disease. Relapsed neuroblastomas harbor chemo-resistant mesenchymal tumor cells and increased expression/activity of the transcriptional co-regulator, the Yes-Associated Protein (YAP). Patients with relapsed neuroblastoma are often treated with immunotherapy such as the anti-GD2 antibody, dinutuximab, in combination with chemotherapy.

The degree of T cell stemness differentially impacts the potency of adoptive cancer immunotherapy in a Lef-1 and Tcf-1 dependent manner.

Generating stem memory T cells (T ) is a key goal for improving cancer immunotherapy. Yet, the optimal way to modulate signaling pathways that enrich T properties remains elusive. Here, we discovered that the degree to which the PI3Kδ pathway is blocked pharmaceutically can generate T cells with differential levels of stemness properties.

B cells imprint adoptively transferred CD8 T cells with enhanced tumor immunity.

Background: Adoptive T cell transfer (ACT) therapy improves outcomes in patients with advanced malignancies, yet many individuals relapse due to the infusion of T cells with poor function or persistence. Toll-like receptor (TLR) agonists can invigorate antitumor T cell responses when administered directly to patients, but these responses often coincide with toxicities. We posited that TLR agonists could be repurposed ex vivo to condition T cells with remarkable potency in vivo, circumventing TLR-related toxicity.

Interventions to increase uptake of the human papillomavirus vaccine in unvaccinated college students: A systematic literature review.

Objective: The purpose of this systematic review is to summarize the best available evidence on interventions that could be implemented in the college environment to increase HPV vaccination uptake in college students who were not previously vaccinated.

Methods: Pubmed, CINAHL, PsycINFO, Cochrane, and EBSCO were searched in December 2017 to identify all literature meeting the following criteria: human subjects, English language, HPV, HPV vaccination, and college. PRISMA recommendations were followed.