Modifications to rhesus macaque TCR constant regions improve TCR cell surface expression.

T cell immunotherapy success is dependent on effective levels of antigen receptor expressed at the surface of engineered cells. Efforts to optimize surface expression in T cell receptor (TCR)-based therapeutic approaches include optimization of cellular engineering methods and coding sequences, and reducing the likelihood of exogenous TCR α and β chains mispairing with the endogenous TCR chains. Approaches to promote correct human TCR chain pairing include constant region mutations to create an additional disulfide bond between the two chains, full murinization of the constant region of the TCR α and β sequences, and a minimal set of murine mutations to the TCR α and β constant regions.

Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy.

An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here we show that adeno-associated virus (AAV)-delivery of two rhesus macaque antibodies to the SIV envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIV239M after discontinuing suppressive ART. Following AAV administration, sustained antibody expression with minimal anti-drug antibody responses was achieved in all but one animal.

Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir.

The rebound competent viral reservoir (RCVR)-virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped-is the primary barrier to eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after intravenous challenge with barcoded SIVmac239 as a means to elucidate the dynamics of RCVR establishment in groups of RMs by creating a multi-log range of pre-ART viral loads and then assessed viral time-to-rebound and reactivation rates resulting from the discontinuation of ART after one year. RMs started on ART on days 3, 4, 5, 6, 7, 9 or 12 post-infection showed a nearly 10-fold difference in pre-ART viral measurements for successive ART-initiation timepoints.

Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-[Formula: see text].

The stem cell hypothesis suggests that there is a small group of malignant cells, the cancer stem cells, that initiate the development of tumors, encourage its growth, and may even be the cause of metastases. Traditional treatments, such as chemotherapy and radiation, primarily target the tumor cells leaving the stem cells to potentially cause a recurrence. Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy where the immune cells are genetically modified to fight the tumor cells.

Modeling the stem cell hypothesis: Investigating the effects of cancer stem cells and TGF-β on tumor growth.

We propose a mathematical model to describe the interaction of cancer stem cells, tumor cells, and the immune system in order to better understand tumor growth in the presence of cancer stem cells. We consider the system in two scenarios: with no-treatment and with a chemotherapy treatment regimen. We develop a system of differential equations, fit the parameters to experimental data, and perform sensitivity and stability analysis.

Equitable mirrors.

Mirror surfaces used in catadioptric sensors are often designed so as to minimize one particular kind of image distortion. In this article we explore some finer properties of equi-areal mirrors, those that feature no area distortion, and we propose novel ways to measure compound forms of distortion. Specifically, we develop new mirror surfaces with large fields of view that simultaneously minimize angular and areal distortion with respect to different cost functions.

Double-mirror catadioptric sensors with ultrawide field of view and no distortion.

We compute a family of double-mirror catadioptric sensors with ultrawide field of view and no distortion. The two concentric mirrors are rotationally symmetric, and the inside mirror is a revolved conic section. The mapping between the object and the image planes was linear, hence the lack of distortion.