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Abbas, A. M.

Publications and source records attributed to Abbas, A. M..

4 recordsLinked to original sources

Multi-point convective delivery overcomes mass transport barriers for myocardial therapeutics

Angiogenesis-promoting macromolecules reduce adverse remodeling and preserve cardiac function in rodents following myocardial infarctions, yet repeatedly fail to translate across length scales in humans. Through mass transport studies in human and swine myocardium, we found that dense, anisotropic myocardial fibers limit therapeutic diffusion and convection to millimeter scales for existing approaches including bolus intramyocardial injections, shear-thinning hydrogels, and epicardial patches. Furthermore, distributions are confined to one dimension along fibers. To increase myocardial drug distribution to centimeter length scales in vivo in swine, we engineered a three-dimensional multi-injection drug delivery array. Our device performs up to 40 simultaneous 120 {micro}L injections of functional macromolecules, hydrogels, or mRNA lipid nanoparticles. Injections are precisely placed in relation to fiber alignment, achieving near-complete coverage of the left ventricular myocardium.

bioengineering↗

A biosecurity baseline for transboundary management of marine biological invasions in the ROPME Sea Area

Marine and brackish-water ecosystems are increasingly degraded by cumulative human pressures, with biological invasions representing a major driver of biodiversity loss, ecosystem disruption, and socio-economic impacts. Effective management requires regionally harmonized and scientifically robust baselines capable of supporting coordinated transboundary decision-making. Here we present the first consolidated marine biosecurity baseline for the Regional Organization for the Protection of the Marine Environment (ROPME) Sea Area, a transboundary region characterized by extreme environmental conditions and increasing biosecurity pressure. A total of 192 species (123 extant and 69 horizon), including birds, fishes, tunicates, invertebrates, plants, and chromists, were systematically reviewed, taxonomically validated, and cross-checked against major databases and Member State inputs. Re-evaluation of a previous regional screening revealed substantial inconsistencies, with 24 species ({approx}18%) requiring status correction or exclusion. The resulting consolidated inventory comprised 130 validated retained species supplemented by 62 additional taxa. Extant species were classified according to biogeographic origin and impact status, whereas horizon species were evaluated based on introduction pathways, environmental suitability, and projected climate trends. Risk screening under current and projected climate conditions identified 39 extant species as very high risk, providing an operational basis for progression to full risk assessment and coordinated regional biosecurity management.

ecology↗

Gastrointestinal delivery of mRNA lipid nanoparticles selectively targets the pancreas

Lipid nanoparticles (LNPs) administered parenterally often show poor localization to the gastrointestinal (GI) tract and pancreas. In addition, patients typically prefer orally administered drugs to those given intravenously. We therefore investigated whether GI delivery, achievable via device mediated microneedle injections applied to buccal, gastric, small intestinal, colonic, or rectal tissues, could simultaneously enhance LNP delivery to the GI and pancreas while avoiding intravenous administration. Using a combined approach of formulation optimization and GI delivery site screening, we found that cationic SM-102 LNPs delivered gastrically achieved 7-fold higher pancreas delivery in rodents than intravenous neutral SM-102 LNPs. With dose optimization, gastric LNPs achieved 6000-fold greater pancreas to liver targeting ratios than intravenous LNPs. These results suggest GI microneedle administration can reprogram LNP biodistribution, thereby expanding therapeutic opportunities for both local and systemic nucleic acid delivery.

bioengineering↗

Lymph node-targeted vaccine boosting of TCR-T cell therapy enhances anti-tumor 1 function and eradicates solid tumors

While T cell receptor (TCR)-modified T cell therapies have shown promise against solid tumors, overall therapeutic benefits in clinical practice have been modest due in part to suboptimal T cell persistence and activation in vivo, alongside the possibility of tumor antigen escape. In this study, we demonstrate an approach to enhance the in vivo persistence and activation of TCR-T cells through combination with Amphiphile (AMP)-vaccination including cognate TCR-T peptides. AMP-modification improves lymph node targeting of conjugated tumor immunogens and adjuvants, thereby coordinating a robust T cell-priming endogenous immune response. Vaccine combination with TCR-T cell therapy provided simultaneous in vivo invigoration of adoptively transferred TCR-T cells and in situ priming of the endogenous anti-tumor T cell repertoire. The resulting induction of an adoptive and endogenous anti-tumor effect led to durable responses in established murine solid tumors refractory to TCR-T cell monotherapy. Protection against recurrence was associated with antigen spreading to additional tumor-associated antigens not targeted by vaccination. Enhanced anti-tumor efficacy was further correlated with pro-inflammatory lymph node transcriptional reprogramming and increased antigen presenting cell maturation, resulting in TCR-T cell expansion and functional enhancement in lymph nodes and solid tumor parenchyma without lymphodepletion. In vitro evaluation of AMP-peptides with matched human TCR-T cells targeting NY-ESO-1, mutant KRAS, and HPV16 E7 illustrated the clinical potential of AMP-vaccination to enhance human TCR-T cell proliferation, activation, and anti-tumor activity. Taken together, these studies provide rationale and evidence to support clinical evaluation of the combination of AMP-vaccination with TCR-T cell therapies to augment anti-tumor activity. SummaryAMP-vaccination targets the lymph nodes to enhance TCR-T cell therapy resulting in solid tumor eradication and durable protection against recurrence.

immunology↗