Frontiers

81. Intratumoral delivery of immunotherapy to treat breast cancer: current development in clinical and preclinical studies

Title Tesim:

Intratumoral delivery of immunotherapy to treat breast cancer: current development in clinical and preclinical studies

Creator:

Zaharoff, David A., Mantooth, Siena M., Abdou, Yara, Upadhaya, Samik, and Saez-Ibañez, Ana Rosa

Date of publication:

2024

Abstract Tesim:

Breast cancer poses one of the largest threats to women’s health. Treatment continues to improve for all the subtypes of breast cancer, but some subtypes, such as triple negative breast cancer, still present a significant treatment challenge. Additionally, metastasis and local recurrence are two prevalent problems in breast cancer treatment. A newer type of therapy, immunotherapy, may offer alternatives to traditional treatments for difficult-to-treat subtypes. Immunotherapy engages the host’s immune system to eradicate disease, with the potential to induce long-lasting, durable responses. However, systemic immunotherapy is only approved in a limited number of indications, and it benefits only a minority of patients. Furthermore, immune related toxicities following systemic administration of potent immunomodulators limit dosing and, consequently, efficacy. To address these safety considerations and improve treatment efficacy, interest in local delivery at the site of the tumor has increased. Numerous intratumorally delivered immunotherapeutics have been and are being explored clinically and preclinically, including monoclonal antibodies, cellular therapies, viruses, nucleic acids, cytokines, innate immune agonists, and bacteria. This review summarizes the current and past intratumoral immunotherapy clinical landscape in breast cancer as well as current progress that has been made in preclinical studies, with a focus on delivery parameters and considerations.

Resource type:

Article

Affiliation Label Tesim:

Joint Department of Biomedical Engineering and UNC Lineberger Comprehensive Cancer Center

DOI:

https://doi.org/10.17615/7yqd-a783

Edition:

Publisher

Identifier:

https://doi.org/10.3389/fimmu.2024.1385484

ISSN:

1664-3224

Journal Title:

Frontiers in Immunology

Journal Volume:

15

Keyword:

Localized delivery, cancer immunotherapy, Neoadjuvant, Intratumoral, and breast cancer

Language Label:

English

License Label:

Attribution 4.0 International

Other Affiliation:

and Cancer Research Institute

Person:

Zaharoff, David A., Mantooth, Siena M., Abdou, Yara, Upadhaya, Samik, and Saez-Ibañez, Ana Rosa

Publisher:

Frontiers

Rights Statement Label:

In Copyright

Source:

3253d1d3-256e-4d76-a1b5-ba0da3fdda9d

82. Interdisciplinary collaborative eye examinations to protect preterm infant neurodevelopment: a quality improvement project

Title Tesim:

Interdisciplinary collaborative eye examinations to protect preterm infant neurodevelopment: a quality improvement project

Creator:

LeBLond, Kristen D., Liu, Tianyi, Clary-Williams, Erika, Ulrich, J. Niklas, McCarty, Dana B., Zbornik-Thompson, Tika, and Go, Michelle S.

Date of publication:

2024

Abstract Tesim:

Introduction Infants born <31 weeks gestational age with birth weight ≤ 1,500 grams receive routine eye examinations to screen for Retinopathy of Prematurity (ROP) while in the Neonatal Intensive Care Unit (NICU) to help prevent vision threatening complications; however, preterm infants’ sensory systems are underdeveloped, and repeated exposure to painful stimuli is associated with worse developmental outcomes.Methods An interdisciplinary NICU team designed a collaborative eye exam model (CEEM) incorporating best practice recommendations for infant pain control during exams. Pain scores and vital signs were recorded before, during, and after exams. Two sets of mixed-effects regression models with a random intercept on infants were established to investigate relationships between the intervention, birth gestational age (BGA), postmenstrual age (PMA), and outcomes associated with painful stimuli. Survey feedback was elicited from NICU stakeholders about the CEEM. Results Thirty standard of care (SC) and 35 CEEM exams of 37 infants were included in final analysis. In infants of the same BGA, the number of desaturation events was significantly reduced in the CEEM group (p = 0.003) and became 1.53 times smaller with each additional week of BGA (p = 0.009). Probability of heart rate recovery within 15 min lowered significantly in the CEEM group (p = 0.04). In SC or CEEM or between infants of the same PMA, no differences were observed for bradycardia, heart rate range, chance of heart rate recovery, or pain scores. Increases in tachycardia (p < 0.001) events and desaturations p = 0.006 were discovered in the CEEM group. When considering interaction effects, the CEEM appeared to reduce the number of desaturations to a greater degree for infants at earliest BGAs with attenuation of this effect with greater BGA. Regarding PMA, bradycardia and tachycardia events were reduced for infants across PMAs in the CEEM, but the effect for tachycardia improves with age, while the effect for bradycardia diminishes with age. Stakeholders agreed that the infant’s eye exam experience and the staff experience was “very much” improved by the CEEM. Discussion Despite variable findings in selected outcome measures, the CEEM was positively viewed by staff. Infants may benefit from the CEEM differently based on BGA and PMA.

Resource type:

Article

Affiliation Label Tesim:

Department of Biostatistics, Department of Ophthalmology, and Division of Physical Therapy

DOI:

https://doi.org/10.17615/xp85-cr20

Edition:

Publisher

Identifier:

https://doi.org/10.3389/fpsyg.2024.1354033

ISSN:

1664-1078

Journal Title:

Frontiers in Psychology

Journal Volume:

15

Keyword:

retinopathy of prematurity, physical therapy, preterm infant, neonatal, occupational therapy, eye examination, and opthalomology

Language Label:

English

License Label:

Attribution 4.0 International

ORCID:

Other Affiliation:

Duke University Hospital, , Monroe Carell Jr. Children’s Hospital at Vanderbilt, and Duke University Medical Center

Person:

LeBLond, Kristen D., Liu, Tianyi, Clary-Williams, Erika, Ulrich, J. Niklas, McCarty, Dana B., Zbornik-Thompson, Tika, and Go, Michelle S.

Publisher:

Frontiers

Source:

90a6e14c-f433-417e-b37c-4462d659d9cc

83. Improved MRI methods to quantify retinal and choroidal blood flow detect decreased blood flow in a model of glaucoma

Title Tesim:

Improved MRI methods to quantify retinal and choroidal blood flow detect decreased blood flow in a model of glaucoma

Creator:

Chernoff, Diane, Honkanen, Robert A., Galenchik-Chan, Andre, Duong, Timothy Q., Jiang, Zhao, Muir, Eric R., and Tomorri, David

Date of publication:

2024

Abstract Tesim:

Purpose: Blood flow (BF) of the retinal and choroidal vasculatures can be quantitatively imaged using MRI. This study sought to improve methods of data acquisition and analysis for MRI of layer-specific retinal and choroidal BF and then applied this approach to detect reduced ocular BF in a well-established mouse model of glaucoma from both eyes. Methods: Quantitative BF magnetic resonance imaging (MRI) was performed on glaucomatous DBA/2J and normal C57BL/6J mice. Arterial spin labeling MRI was applied to image retinal and choroidal BF using custom-