CHEMICAL & BIOMOLECULAR ENGINEERING
Published in Cancer Research (2021)
In this review, my colleagues and I review the landscape of using macrophages as anticancer treatments. In addition to highlighting efforts to alter the TME by targeting tumor-associated macrophages, we focus on approaches which directly engineer macrophages to perform anti-tumor functions. CAR macrophages, which was a previous paper, are discussed in depth and contrasted with CAR T cells for the treatment of solid tumors.
Find this paper on PubMed!
Published in Nature Biotechology (2020)
I was fortunate enough to be a co-author on this paper with the co-founder of Carisma Therapeutics, Mike Klichinsky. In this paper, we showed that macrophages could be transduced with a chimeric Ad5f35 adenovirus to express a first generation CAR. This CAR is active and causes the phagocytosis and killing of target postive tumor cells, while also stimulating pro-inflamatory cytokine release upon antigen stimulation. This promotes tumor clearance in vitro and in vivo, while also converting the TME from “cold” to “hot.”
Published in: Biophysical Journal (2019)
This paper, written by my collaborator Alex Buffone, extends the paradigm of upstream migration in immune cells to neutrophils. Previous studies had suggested that these cells did not migrate upstream on ICAM-1 like other immune cells. Through the use of blocking antibodies and engineered surfaces, we proved that these cells will migrate upstream if Mac-1 is blocked. We believe that Mac-1 acts as a sink for ICAM-1, which prevents the engagement of LFA-1 and the resulting upstream migration.
Published in: Integrative Biology (2019)
In this paper, we took a previously published model of T cell trafficking and extended it to include the functions of kindlin-3, a protein which mediates the conversion of LFA-1 from an intermediate affinity form to the high affinity form used to arrest on the endothelium. Our simulations predicted that lymphocyte adhesion would be hypersensitive to the level of kindlin-3, which we then predicted through genetic perturbation of a model cell line along with comparisons to literature. Especially exciting for us was that the predictions were quantitatively accurate. This suggests that Adhesive Dynamics simulations can used to predict the effect of changing protein levels or kinetic constants on the ability of cells to adhere to endothelium.
The 2018 AIChE national meeting in Pittsburgh was a really great opportunity to see some of the work that is going to be impacting us in the future. There was some really great work on biomaterials on Monday and Tuesday. Wednesday and Thursday had some absolutely amazing work on anti-cancer therapeutics, as well as computational models of biological systems.
I especially want to thank everyone that came out to see my presentation, which will be posted here as soon as the manuscript is published!
I am excited for the upcoming 2018 AIChE National Meeting happening next week in Pittsburgh, PA. Please be sure to stop by my oral presentation on Wednesday, October 31 at 3:30 PM. The talk is titled “A Quantitative Analysis of Integrin Activation on T Cell Homing” and is part of the Integrative Systems Biology session. I hope to see you there! Please feel free to contact me if you need additional information.
Today, of course, was the 2018 Penn CBE Graduate Student Symposium. There was quite a bit of really great discussions about all kinds of research going on in the department. I especially want to thank everyone that came by my poster and listened to my talk. As the work presented is still unpublished, I will not be posting a copy of the presentation immediately. However, you can be sure that once it is published it will be posted.
It finally feels as though I am getting the hang of this, as this time the paper I’m posting is actually new! I have a new second-author paper with Amy Bendell in Annals of Biomedical Engineering about substrate geometry sensing in dentritic cells. I’ve posted a short description of the work here. I hope you take the time to read it. It’s really an awesome story!
Published in: Annals of Biomedical Engineering (2018)
This paper, which I am a second author on, was originally going to be about the forces exerted by dendritic cells under certain conditions. However, we found that on the force detectors the cells migrated differently compared to cells on a flat surface. What we found instead was evidence that dendritic cells can sense the geometry of the substrate they are on. For example, we found rings of actin around the tips of posts sticking up from the surface, but did not see similar rings on flat surfaces containing adhesive ligands. Overall, quite the interesting paper!
Nicholas R. Anderson 