Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma.

Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.

First Measurement: Proactive Immune Cell Sparing in Radiation Therapy.

Purpose: Radiation Therapy (RT) can modulate the immune system and generate anti-tumor T cells. However, this anti-tumor-activity is countered by radiation-induced immunosuppression (RIIS). Clinical advantages of proactively sparing RT dose to immune rich organs have not previously been evaluated.

Optimizing a Novel Smartphone App to Prevent Postpartum Depression Adapted From an Evidence-Based Cognitive Behavioral Therapy Program: Qualitative Study.

Background: Low-income pregnant patients are at high risk of postpartum depression (PPD). Mothers and Babies (MB) is a cognitive behavioral therapy-based program that prevents up to 50% of de novo PPD when provided in person to low-income Spanish- and English-speaking people who are pregnant without depression. MB is limited by the need for trained personnel to support it.

Impact of CRISPR in cancer drug discovery.

Precision gene editing enables massively parallel identification of cancer-promoting genes.

Circulating Interleukins as Biomarkers in Non-Small Cell Lung Cancer Patients: A Pilot Study Compared to Normal Individuals.

Identifying biomarkers in non-small cell lung cancer (NSCLC) can improve diagnosis and patient stratification. We evaluated plasmas and sera for interleukins (IL)-11, IL-6, IL-8, IL-17A, and IL-33 as biomarkers in primary NSCLC patients undergoing surgical treatment against normal volunteers. Exhaled-breath condensates (EBCs), a potential source without invasive procedures, were explored in normal individuals.

Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T.

Unlabelled: Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration-resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival after sipuleucel-T (sip-T) therapy, an FDA-approved, autologous cell therapy. We hypothesized these differences may be explained by previously reported ancestral differences in pattern recognition receptor signaling, which broadly governs innate inflammation to control adaptive immune cell activation, chemotaxis, and functionality.

Looking ahead to CD3, T-cell engager bispecific antibodies for hematological malignancies.

Introduction: Since the approval of the bispecific antibody blinatumomab in 2017 for the treatment of acute lymphoblastic leukemia in relapse, the development of numerous bispecific antibody constructs has dramatically expanded in hematologic malignancies. Many have recently received Food Drug Administration and European Medicines Agency approvals in various stages of treatment for lymphomas, leukemias, and multiple myeloma.

Areas Covered: The purpose of this review is to provide an overview of bispecific antibody treatment including the mechanisms leading to effector T cells targeting tumor-associated antigens, the treatment indications, efficacies, toxicities, and challenges of the different constructs.

Use of High-Fidelity Simulation as an Adjunct to Basic Life Support Training To Promote Team-Based Resuscitation Skills: A Mixed-Methods Pilot Study.

Introduction The 2020 American Heart Association's (AHA) Basic Life Support (BLS) curriculum focuses on cardiac arrest resuscitation with one or two rescuers, providing only limited opportunities to develop higher-level skills such as leadership, communication, and debriefing. This mixed-methods pilot study evaluated whether supplementing the traditional Heartcode BLS course with a high-fidelity teamwork simulation session improved mastery of these higher-level skills. Methods Twenty-four first-year medical students completed the pilot training during sessions offered in February and May of 2023.

Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate-Resistant Prostate Cancer.

Unlabelled: Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored. Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers before and after treatment.

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection - Derivation of a clinical risk score.

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006-2023.

Adjunctive Pascolizumab in Rifampicin-Susceptible Pulmonary Tuberculosis: Proof-of-Concept, Partially-Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Trial.

Background: Interleukin 4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanized anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment.

Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells.

Background: The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.

Methods: The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1).

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

Purpose: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy.

Methods: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ.

Iron deficiency in healthy, term infants aged five months, in a pediatric outpatient clinic: a prospective study.

Background: Iron deficiency (ID) is prevalent in Malaysian children. The incidence of ID in infants under 6 months of age is unknown. Our aim was to determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in healthy, term infants aged below 6 months in our hospital population.

Targeting GD2-positive Refractory/Resistant Neuroblastoma and Osteosarcoma with Anti- CD3 x Anti-GD2 Bispecific Antibody Armed T cells.

Background: Since treatment of neuroblastoma (NB) with anti-GD2 monoclonal antibodies provides a survival benefit in children with minimal residual disease and our preclinical study shows that anti-CD3 x anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs) were highly cytotoxic to GD2+ cell lines, we conducted a phase I/II study in recurrent/refractory patients to establish safety and explore the clinical benefit of GD2BATs.

Methods: The 3+3 dose escalation study (NCT02173093) phase I involved 9 evaluable patients with NB (n=5), osteosarcoma (OST) (n=3), and desmoplastic small round cell tumors (DSRCT) (n=1) with twice weekly infusions of GD2BATs at 40, 80, or 160 x 10 GD2BATs/kg/infusion with daily interleukin 2 (300,000 IU/m) and twice weekly granulocyte-macrophage colony stimulating factor (250 μg/m). Phase II portion of the trial was conducted in patients with NB at the dose 3 level of 160 x 10 GD2BATs/kg/infusion but failed to enroll the planned number of patients.

Breastfeeding Prevalence and Factors Affecting Breastfeeding Duration Among Urban Multi-ethnic Malaysian Mothers: A Single-Center University Hospital Study.

Breastfeeding rates in urban Malaysian mothers are below World Health Organization (WHO) targets. Our prospective survey identified breastfeeding prevalences at 3, 6, and 12 months of 85.5%, 77%, and 60%, respectively.

Novel anti-CD30/CD3 bispecific antibodies activate human T cells and mediate potent anti-tumor activity.

CD30 is expressed on Hodgkin lymphomas (HL), many non-Hodgkin lymphomas (NHLs), and non-lymphoid malignancies in children and adults. Tumor expression, combined with restricted expression in healthy tissues, identifies CD30 as a promising immunotherapy target. An anti-CD30 antibody-drug conjugate (ADC) has been approved by the FDA for HL.

From "disappointing" to "fantastic": Women's experiences with labor induction in a U.S. tertiary hospital.

Objective: The series of interventions that comprise labor induction shape patient experiences; however, patient perceptions are not always considered when structuring the process of care. Through qualitative interviews, we elucidated women's expectations and experiences regarding labor induction.

Methods: Labor induction patients were recruited from a United States tertiary care hospital's postpartum mother-baby unit and invited to participate in semi-structured qualitative interviews.

The Prevalence and Determinants of Child Hunger and Its Associations with Early Childhood Nutritional Status among Urban Poverty Households during COVID-19 Pandemic in Petaling District, Malaysia: An Exploratory Cross-Sectional Survey.

Child hunger was prevalent during the COVID-19 pandemic, but the extent, determinants, and impact on pre-school children aged 6 months to 7 years old from Malaysian urban poor households are still unknown. This exploratory cross-sectional study was performed between July 2020 and January 2021 at the Lembah Subang People Housing Project, Petaling. The households' food security status was assessed using the previously validated Radimer/Cornell questionnaire, and the children's anthropometric measurements were taken.

Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities.

The degradation tag (dTAG) system for target protein degradation can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack of reversibility, low specificity, and the inability to titrate dosage. These drawbacks can make it difficult to compare toxicity resulting from genetic and pharmacological interventions, especially in vivo. Because the dTAG system has not been studied extensively in vivo, we explored the use of this system to study the physiological sequalae resulting from CDK2 or CDK5 degradation in adult mice.

Tumor cell heterogeneity drives spatial organization of the intratumoral immune response in squamous cell skin carcinoma.

Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy and an inferior anti-tumor immune response. The underlying mechanism of this association is unknown. To address this question, we modeled heterogeneous tumors comprised of a pro-inflammatory ("hot") and an immunosuppressive ("cold") tumor population, labeled with YFP and RFP tags respectively to enable precise spatial tracking.