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Background: The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system. Methods: Electronic health records were used to identify 46,094 women aged 30–65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test. Results: Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: 0.93 – 0.96). Further, those with indigent healthcare plans had a higher prevalence of being UTD when compared to those with private insurance (aPR: 1.10, 95% CI: 1.09 – 1.12), while all other health insurance plans were associated with lower UTD screening when compared to private insurance. Conclusions: These findings suggest screening differences within the Hispanic population, highlighting the need for disaggregated research assessing heterogeneity within racial/ethnic groups, specifically among Hispanic populations. [ABSTRACT FROM AUTHOR]

Purpose: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC. Materials and methods: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy. Results: All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion. Conclusion: MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC. [ABSTRACT FROM AUTHOR]

Objective: To assess knowledge, attitudes, and perceived barriers (KAP) regarding e‐cigarette use counselling among adolescent healthcare clinical staff in an urban system, and to compare results between providers and rooming staff. Methods: Primary care clinical staff (n = 169) completed an anonymous survey. Descriptive statistics and Chi‐square tests were used to summarize data and compare KAP between medical providers and rooming staff. Results: Staff wanted to learn more about e‐cigarettes (87.6%). The most common knowledge deficits were how to use the 5As + 5Rs model for tobacco cessation counselling (66.7%) and the chemical content of e‐liquids (55.4%), with no differences across groups. Overall, 58% of providers expressed confidence in their ability to talk with adolescent patients about e‐cigarette use. The most common barriers to counselling were low knowledge about e‐cigarettes (74.0%) and how to refer adolescent patients for cessation support (43.8%). Conclusions: Provider and rooming staff expressed similar educational needs surrounding e‐cigarettes, counselling, and treatment for adolescent patients. Clinical staff expressed confidence in their ability to affect change. There were no differences in the identified knowledge gaps or barriers to care between rooming staff and providers, suggesting that the same educational format can be used to target both groups. [ABSTRACT FROM AUTHOR]

Simple Summary: Most children infected with HIV live in Sub-Sahara Africa (SSA). These children are at risk of cancers related to HIV infection, but the degree of this risk and how it is influenced by antiretroviral therapy (ART) is unknown. In this study, we determined the subtypes, incidence, and risk factors of cancers in children with HIV in SSA and receiving ART with the goal of learning how we may prevent these cancers. We found that Kaposi sarcoma and lymphoma are the most common, comprising about 77% and 19% of cancers in these children, respectively. For every 100,000 person-years, 47.6 children developed cancer. Waiting to start ART until after 2 years old and having had severe immunosuppression were the two biggest risk factors for cancer that we identified. The findings justify the recommendations to start children on ART as soon as they are diagnosed with HIV regardless of their CD4 immune status. Approximately 91% of the world's children living with HIV (CLWH) are in sub-Saharan Africa (SSA). Living with HIV confers a risk of developing HIV-associated cancers. To determine the incidence and risk factors for cancer among CLWH, we conducted a nested case-control study of children 0–18 years from 2004–2014 at five centers in four SSA countries. Incident cases of cancer and HIV were frequency-matched to controls with HIV and no cancer. We calculated the incidence density by cancer type, logistic regression, and relative risk to evaluate risk factors of cancer. The adjusted incidence density of all cancers, Kaposi sarcoma, and lymphoma were 47.6, 36.6, and 8.94 per 100,000 person-years, respectively. Delayed ART until after 2 years of age was associated with cancer (OR = 2.71, 95% CI 1.51, 4.89) even after adjusting for World Health Organization clinical stage at the time of enrolment for HIV care (OR = 2.85, 95% CI 1.57, 5.13). The relative risk of cancer associated with severe CD4 suppression was 6.19 (p = 0.0002), 2.33 (p = 0.0042), and 1.77 (p = 0.0305) at 1, 5, and 10 years of ART, respectively. The study demonstrates the high risk of cancers in CLWH and the potential benefit of reducing this risk by the early initiation of ART. [ABSTRACT FROM AUTHOR]

Background/aim: Chimeric antigen receptor (CAR) T cells with tumor specificity are being increasingly investigated. Phase I trials are the first step of testing for safety of novel CAR-T therapy to determine the maximum tolerated dose (MTD). Several dose escalation methods have been developed over time including rule-based, model-based, and model-assisted designs. The goal of this project is to overview the phase I designs used in current CAR-T trials., Materials and Methods: We searched PubMed for peer-reviewed literature published between January 1, 2015 and December 31, 2021. The search was limited to human studies in the English language using the keywords "CAR-T phase I", "clinical trials", and "full text"., Results: One hundred nine papers with at least partial phase I components were included for analysis. 31.2% of the trials used the traditional 3+3 or a variation of said design, and 60.6% did not mention the dose escalation design. The majority of the manuscripts (59.6%) did not report cohort size while 19.3% did not specify the timing of evaluation. Although most of the studies were registered with CT.gov, only 33.9% had any results submitted or posted to CT.gov These trends persisted even in manuscripts published in journals with high impact factors., Conclusion: Standardizing the publication criteria and providing basic elements of phase I clinical trials are critical to ensure high quality of manuscripts. With the quick development and high costs of CAR-T cell therapy, adoption of advanced designs such as model-based and model-assisted should increase to improve efficiency of clinical trials., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in the world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)-expressing T cells induce robust antitumor responses in patients with hematologic malignancies but have limited efficacy in patients with solid tumors, including HCC. IL15 and IL21 promote T-cell expansion, survival, and function and can improve the antitumor properties of T cells. We explored whether transgenic expression of IL15 and/or IL21 enhanced glypican-3-CAR (GPC3-CAR) T cells' antitumor properties against HCC. We previously optimized the costimulation in GPC3-CARs and selected a second-generation GPC3-CAR incorporating a 4-1BB costimulatory endodomain (GBBz) for development. Here, we generated constructs encoding IL15, IL21, or both with GBBz (15.GBBz, 21.GBBz, and 21.15.GBBz, respectively) and examined the ability of transduced T cells to kill, produce effector cytokines, and expand in an antigen-dependent manner. We performed gene-expression and phenotypic analyses of GPC3-CAR T cells and CRISPR-Cas9 knockout of the TCF7 gene. Finally, we measured GPC3-CAR T-cell antitumor activity in murine xenograft models of GPC3 + tumors. The increased proliferation of 21.15.GBBz T cells was at least in part dependent on the upregulation and maintenance of TCF-1 (encoded by TCF7 ) and associated with a higher percentage of stem cell memory and central memory populations after manufacturing. T cells expressing 21.15.GBBz had superior in vitro and in vivo expansion and persistence, and the most robust antitumor activity in vivo These results provided preclinical evidence to support the clinical evaluation of 21.15.GPC3-CAR T cells in patients with HCC., (©2020 American Association for Cancer Research.)