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Are “backpack” armed macrophages the next big thing in cellular immunotherapy?

Image credit: https://wyss.harvard.edu/news/backpacks-boost-immune-cells-ability-to-kill-cancer/

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Subash Chapagain
Subash Chapagain Nov 30, 2020

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[4]Shields, C. W., Evans, M. A., Wang, L. L.-W., Baugh, N., Iyer, S., Wu, D., Zhao, Z., Pusuluri, A., Ukidve, A., Pan, D. C., & Mitragotri, S. (2020). Cellular backpacks for macrophage immunotherapy. Science Advances, 6(18), eaaz6579. https://doi.org/10.1126/sciadv.aaz6579

[5]Doshi, N., Swiston, A. J., Gilbert, J. B., Alcaraz, M. L., Cohen, R. E., Rubner, M. F., & Mitragotri, S. (2011). Cell-Based Drug Delivery Devices Using Phagocytosis-Resistant Backpacks. Advanced Materials, 23(12), H105–H109. https://doi.org/10.1002/adma.201004074

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Materials that can be used to construct the backpack

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Shubhankar Kulkarni
Shubhankar Kulkarni Dec 16, 2020

[1]Yeste A, Nadeau M, Burns EJ, Weiner HL, Quintana FJ. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc Natl Acad Sci [Internet]. 2012 Jul 10;109(28):11270–5. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.1120611109

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[4]Turley DM, Miller SD. Peripheral Tolerance Induction Using Ethylenecarbodiimide-Fixed APCs Uses both Direct and Indirect Mechanisms of Antigen Presentation for Prevention of Experimental Autoimmune Encephalomyelitis. J Immunol [Internet]. 2007 Feb 15;178(4):2212–20. Available from: http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.178.4.2212

[5]Prasad S, Kohm AP, McMahon JS, Luo X, Miller SD. Pathogenesis of NOD diabetes is initiated by reactivity to the insulin B chain 9-23 epitope and involves functional epitope spreading. J Autoimmun [Internet]. 2012 Dec;39(4):347–53. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0896841112000480

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General comments

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Shubhankar Kulkarni
Shubhankar Kulkarni2 months ago
A few other questions:
1. Is this a preventive therapy? If yes, I imagine the therapy will be needed to be given perpetually (since the life of the backpack is about 5 days? So, is a constitutive pro-inflammatory state advisable? Since you mention that anti-inflammatory molecules can be used to treat inflammatory diseases, will the pro-inflammatory ones lead to those same diseases?
2. Do these backpacks accumulate in different organs in the body? Since they are synthetic, they might create additional problems. Are they thrown out by the body in some way? If yes, that solves our problem.
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Subash Chapagain
Subash Chapagain2 months ago
Shubhankar Kulkarni The approach seems to be more likely to be curative rather than preventive (however it would be interesting to see if we could load a certain portion of individual's macrophages beforehand and then try to see how much of preventive effects they might have which can surely be tested in mouse models if I am not wrong). In the context of carcinomas, it indeed would be crucial to objectify the scales to which the specific pro or anti-inflammatory molecules would give the presumed effects like you said.

As far as the bio-accumulation is concerned, they have reported no significant complexities related to it; the particles have been deemed absolutely biocompatible.