Understanding the Role of the Immune System in Improving Tissue Regeneration Proceedings of a Workshop (2022) / Chapter Skim
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8 Harnessing the Immune System to Improve Patient Outcomes
8 Harnessing the Immune System to Improve Patient Outcomes
Pages 113-126
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From page 113... ...
• The complexity of both regenerative medicine products and the im mune system presents challenges in predicting the human immune response to therapeutics and in assessing their safety. (Brooks)
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From page 114... ...
The objective of the sixth and final session of the workshop was to explore areas of clinical therapeutic need amenable to becoming clinical trial candidates. Candidates of particular interest are those that demonstrate proof of principle of a specific therapeutic for clinical indication and that address the immune system's role in improving tissue regeneration.
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From page 115... ...
Wynn expressed his interest in harnessing those mechanisms as an opportunity to reverse fibrosis and restore tissue homeostasis and to better understand how fibrosis impedes regeneration. A rich area of opportunity lies at the convergence of "domain expertise" in mass spectrometry profiling, metabolomics, and regenerative medicine, said Edward Botchwey, an associate professor in the Department of Biomedical Engineering at the Georgia Institute of Technology.
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From page 116... ...
McFarland emphasized the importance of the patient experience in translating science to cures, noting that scientists can become enthralled with the science and lose sight of the patient experience. Possible Roles of Healing and the Immune System in Regenerative Medicine McFarland asked the panelists about opportunities on the horizon to harness the immune system to improve tissue regeneration and patient experience.
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From page 117... ...
Convening is one way to share important advances in manipulating cellular senescence, harnessing the pathways of inflammation resolution, and understanding functional roles and spatial organizations of immune cells and other cell types. He noted current progress in technologies to interpret single-cell data, in ex vivo model systems to control the arrangement of cells in three dimensions, and in engineering biomaterials to present biomolecules to immune cells that alter their function.
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From page 118... ...
Given that transplanted therapeutic cells should be not only shielded from the immune system but also able to replicate, McFarland asked Schrepfer whether there is a risk of oncology carcinogenesis and how risk can be mitigated if the cells are shielded from normal antitumor surveillance. When immune evasion or immune tolerance is in effect, implanted therapeutic cells cannot be controlled using the immune system.
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From page 119... ...
She intends to debrief her team at the FDA on new approaches in use and products shared during the workshop that could potentially enter clinical trials in coming years. Emerging Areas in Regenerative Medicine Discussed by Individual Speakers The field of regenerative medicine requires prolonged focus, said Wynn, noting that after three decades of work on the mechanisms of fibrosis, therapeutics that effectively treat and slow the progression of severe outcomes of fibrotic disease have not been forthcoming.
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From page 120... ...
At that time, Carl June, a pioneer in chimeric antigen receptor T-cell therapy, talked about the potential to enhance the capabilities of the immune system using tumor-infiltrating lymphocytes, but the promise was not fully realized. Over 15 years later, Memorial Sloan Kettering and the National Institutes of Health achieved this goal of eliciting a positive immune response.
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From page 121... ...
Finally, Sadelain discussed anti-cancer CAR T immunotherapies featuring engineered T cells, which he described as "living drugs." Lumelsky reiterated that CAR T therapies may be a future tool for removing senescent cells and modulating tissue regeneration. Endogenous Mechanisms of Repair and their Modulation The workshop also featured approaches that do not require exogenous cell injection; rather, the strategies manipulate endogenous modulators of cell processes to repair or build new tissue, Lumelsky summarized.
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From page 122... ...
Lumelsky expressed her hope that someday many conditions will be amenable to therapies that manipulate endogenous modulators of cell regeneration, cell degeneration, and aging and that exogenous cell injection may no longer be necessary for building new tissues.
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From page 123... ...
For instance, Medzhitov introduced concepts of tissue homeostasis and division of labor among different cell types. These concepts could serve as models for ideas being developed in tissue regeneration, suggested Potter.
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From page 124... ...
Combining regenerative medicine, immunology, and biomaterial design, the field of regenerative immunology has the potential to both promote endogenous tissue regeneration and affect the survival and regeneration of exogenous cell-based therapies, Lumelsky remarked in response to Elisseeff's work.
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From page 125... ...
In this era, big data and collaboration across sciences will be important in achieving the creation of economically feasible, curative therapies that can be distributed to diverse populations, said McFarland. He added that this can be carried out in a way that decreases the disparity that has been inherent in clinical services.
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