Bonamino, M. H. | Search bioRxiv

bioRxiv2021

Oral Lichen Planus and its relation with Oral Squamous Cell Carcinoma: new insights into the potential for malignant transformation

Oral Lichen Planus (OLP) is a chronic inflammatory disorder of unknown etiology. However, evidence suggests that it consists of an immunological process that leads to degeneration of the keratinocytes in the basal layer of the oral mucosa. Despite being recognized by WHO as a potentially malignant disorder with progression to oral squamous cell carcinoma (OSCC), the relationship between both pathologies is still controversial. Different studies have investigated factors associated with the potential for malignant transformation of OLP but it remains unclear. Through a bioinformatics approach, we investigated similarities in gene expression profiles of OLP and OSCC in early and advanced stages. Our results revealed gene expression patterns related to processes of keratinization, keratinocyte differentiation, cell proliferation and immune response in common between OLP and early and advanced OSCC, with the cornified envelope formation and antigen processing cross-presentation pathways in common between OLP and early OSCC. Together, these results reveal that key genes such as PI3, SPRR1B and KRT17, in addition to genes associated with different immune processes such as CXCL-13, HIF1A and IL1B may be involved in this oncogenic process. In addition, we performed an analysis of differentially and co-expressed genes and proposed putative therapeutic targets and associated drugs.

bioinformatics↗

bioRxiv2019

DEVELOPMENT OF CAR-T CELL THERAPY FOR B-ALL USING A POINT-OF-CARE APPROACH

Recently approved by the FDA and European Medicines Agency, CAR-T cell therapy is a new treatment option for B-cell malignancies. Currently, CAR-T cells are manufactured in centralized facilities and face bottlenecks like complex scaling up, high costs and logistic operations. These difficulties are mainly related to the use of viral vectors and the requirement to expand CAR-T cells to reach the therapeutic dose. In this paper, by using Sleeping Beauty-mediated genetic modification delivered by electroporation, we show that CAR-T cells can be generated and used without the need for ex vivo activation and expansion, consistent with a point-of-care (POC) approach. Our results show that minimally manipulated CAR-T cells are effective in vivo against RS4;11 leukemia cells engrafted in NSG mice even when inoculated after only 4 hours of gene transfer. In an effort to better characterize the infused CAR-T cells, we show that 19BBz T lymphocytes infused after 24h of electroporation (where CAR expression is already detectable) can improve the overall survival and reduce tumor burden in organs of mice engrafted with RS4;11 or Nalm-6 B cell leukemia. A side-by-side comparison of POC approach with a conventional 8-day expansion protocol using Transact beads demonstrated that both approaches have equivalent antitumor activity in vivo. Our data suggests that POC approach is a viable alternative for the generation and use of CAR-T cells, overcoming the limitations of current manufacturing protocols. Its use has the potential to expand CAR immunotherapy to a higher number of patients, especially in the context of low-income countries.

immunology↗