Lymph-directed immunotherapy – Harnessing endogenous lymphatic distribution pathways for enhanced therapeutic outcomes in cancer

Feeney, Orlagh M.; Gracia, Gracia; Brundel, Daniel H.S.; Trevaskis, Natalie L.; Cao, Enyuan; Kaminskas, Lisa M.; Porter, Christopher John

doi:10.1016/j.addr.2020.10.002

Cited by 21 publications

(20 citation statements)

References 232 publications

(353 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, greater than 90% of the lymphocyte pool resides within the lymphatic system, approximately 50% of which are localized in the intestinal lymph and lymphoid tissues 57 . The ability to modulate targets using lymphatically-directed small molecules creates the prospect of forming an inhospitable environment to disrupt aberrant signal transduction, cellular trafficking, and immune cell networks, thereby reducing viability within the ‘protective’ lymphoid niche 58 , 59 . Thus, lymphatic targeting of lymphoid or cancer cells represent promising clinical applications for development of lymphatropic therapy to address challenges in auto-immunity and metastasis.…”

Section: Discussionmentioning

confidence: 99%

A lymphatic-absorbed multi-targeted kinase inhibitor for myelofibrosis therapy

et al. 2022

View full text Add to dashboard Cite

Activation of compensatory signaling nodes in cancer often requires combination therapies that are frequently plagued by dose-limiting toxicities. Intestinal lymphatic drug absorption is seldom explored, although reduced toxicity and sustained drug levels would be anticipated to improve systemic bioavailability. A potent orally bioavailable multi-functional kinase inhibitor (LP-182) is described with intrinsic lymphatic partitioning for the combined targeting of phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways without observable toxicity. We demonstrate selectivity and therapeutic efficacy through reduction of downstream kinase activation, amelioration of disease phenotypes, and improved survival in animal models of myelofibrosis. Our further characterization of synthetic and physiochemical properties for small molecule lymphatic uptake will support continued advancements in lymphatropic therapy for altering disease trajectories of a myriad of human disease indications.

show abstract

Section: Discussionmentioning

confidence: 99%

A lymphatic-absorbed multi-targeted kinase inhibitor for myelofibrosis therapy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, although a considerable number of patients respond well to treatment, there are still some patients who do not respond, and some cancers cannot be treated with these therapies. 29,30 Recently, with the development of genomics and transcriptomics, studies about IRGs or prognostic signatures in cancers, including melanoma, have been increasingly reported. In one study of melanoma, Huang et al, 16 first found that 63 IRGs were associated with the OS of patients.…”

Section: Discussionmentioning

confidence: 99%

<p>Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma</p>

Xie¹,

Dong²,

Jiang³

et al. 2020

CCID

View full text Add to dashboard Cite

Introduction Skin cutaneous melanoma (SKCM) is a common skin malignancy worldwide, and its metastasis and mortality rates are high. The molecular characteristics exhibited by tumor–immune interactions have drawn the attention from researchers. Therefore, increased knowledge and new strategies to identify effective immune-related biomarkers may improve the clinical management of SKCM by providing more accurate prognostic information. Patients and Methods In this study, we established a prognostic immune-related gene pair (IRGP) signature for predicting the survival of SKCM patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided gene expression profiles together with clinical information, and the samples were randomly divided into three groups including the training, testing, and validation datasets. The regression model of least absolute shrinkage and selection operator (LASSO) helped to identify a 13-IRGP signature with a significant relation to the survival of SKCM patients. Results The training, TCGA, and independent sets have an average value of area under the curve of 0.79, 0.76, and 0.82, respectively. In addition, this 13-IRGP signature can noticeably divide SKCM patients into high-risk group and low-risk group with significantly different prognoses. Many biological activities such as gene family were enriched among the genes in our IRGP signature. While analyzing the risk signature and clinical characteristics, there was a large difference in the risk score between T stage and tumor stage grouping. Finally, we constructed a nomogram and forest plots of the risk score and clinical features. Conclusion In summary, we developed a robust 13-IRGP prognostic signature in SKCM, which can identify and provide new insights into immunological biomarkers.

show abstract

“…For example, the MPER-656 liposome vaccine developed by NIAID to treat HIV infection is in phase I clinical research, and the GLA-LSQ liposome vaccine developed by NIAID to treat Plasmodium Falciparum Infections is also in phase I clinical trial. Moreover, in the treatment of lung cancer, glioma, ovarian cancer, and cervical cancer, lipid-based vaccine delivery systems are in accelerating clinical research and development [188] , [189] .…”

Section: Clinical Vaccine Delivery Systemsmentioning

confidence: 99%