THE ROLE OF TRANSFERRIN RECEPTOR (CD71) IN PHOTODYNAMIC THERAPY OF ACTIVATED AND MALIGNANT LYMPHOCYTES USING THE HEME PRECURSOR δ‐AMINOLEVULINIC ACID (ALA)
Abstract
Endogenously generated protoporphyrin IX (PpIX) from exogenous ALA can be an effective photosensitizer. PpIX accumulation is inversely dependent on available intracellular iron, which is required for the conversion of PpIX to heme. Iron also is necessary for cell replication. Since iron can be toxic, intracellular iron levels are tightly controlled. Activated and proliferating cells respond to the demand for intracellular iron by upregulating membrane expression of the transferrin receptor (CD71) which is needed for iron uptake. We predicted that activated lymphocytes (CD71 +) would preferentially accumulate PpIX because of their lower intracellular iron levels and because of competition for iron between ALA‐induced heme production and cellular growth processes. Thus, the CD71+ cells could serve as PDT targets. Stimulation of human peripheral blood lymphocytes (PBL) with the mitogens, phytohemagglutinin A, concanavalin A and pokeweed prior to incubation with ALA results in PpIX accumulation correlating with level of activation. Activated lymphocytes expressing high levels of surface CD71 transferrin receptors generated more PpIX than those with low CD71 expression. Incubating activated cells in transferrin depleted medium (thereby decreasing the iron availability) further increased PpIX levels. Malignant, CD71 + T lymphocytes from a patient with cutaneous T‐cell lymphoma (CTCL)/Sezary syndrome also accumulated increased PpIX levels in comparison to norma] lymphocytes. PDT of activated lymphocytes and Sezary cells after ALA incubation demonstrated preferential killing compared to normal, unstimulated PBL. These findings suggest a possible mechanism for the selectivity of ALA PDT for activated CD71+ cells. They also indicate a clinical use for ALA‐PDT in therapy directed towards the malignant lymphocytes in leukemias and lymphomas, and as animmunomodulatory agent.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ALA-PDT is able to selectively kill activated T cells including CD4 and CD8 cells.
“It is worth noting that ALA-PDT is able to selectively kill activated T cells including CD4 and CD8 cells.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [159]
PpIX is preferentially accumulated only in activated T cells but not resting T cells without activation after ALA incubation, resulting in the selective killing of activated T cells by PDT.
“This is because PpIX is preferentially accumulated only in activated T cells but not resting T cells without activation after ALA incubation, resulting in the selective killing of activated T cells by PDT [159,160].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [159]
Cites
Photodynamic therapy with endogenous protoporphyrin
Kennedy, J. C., Pottier, R. H., & Pross, D. C. (1990) · Journal of Photochemistry and Photobiology B: Biology · doi:10.1016/1011-1344(90)85083-9 · Cited by 1,509 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
5-Aminolevulinic Acid-Based Photodynamic Therapy: Principles and Experimental Research
Peng, Q., Berg, K., Moan, J., Kongshaug, M., & Nesland, J. M. (1997) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1997.tb08549.x · Cited by 615 · see citing works
Berg, K., Anholt, H., Bech, Ø., & Moan, J. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.423 · Cited by 142 · see citing works
Liu, W., Baer, M. R., Bowman, M. J., Pera, P., Zheng, X., Morgan, J., Pandey, R. A., & Oseroff, A. R. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1599 · Cited by 136 · see citing works
Self-citation5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy
Howley, R., Chandratre, S., & Chen, B. (2023) · Bioengineering · doi:10.3390/bioengineering10040496 · Cited by 33 · see citing works
Darvekar, S., Juzenas, P., Oksvold, M., Kleinauskas, A., Holien, T., Christensen, E., Stokke, T., Sioud, M., & Peng, Q. (2020) · Cancers · doi:10.3390/cancers12020377 · Cited by 16 · see citing works
- Authors
- Rittenhouse‐Diakun, K., Leengoed, H. V., Morgan, J., Hryhorenko, E., Paszkiewicz, G., Whitaker, J. E., & Oseroff, A. R.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Oseroff, A. R.
- ORCID
- Morgan, J.
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 1995-05
- Volume
- 61
- Issue
- 5
- Pages
- 523-528
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- OpenAlex
- W2054301677
- Cited by
- 124
- References
- 1
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca045767-06)
- National Cancer Institute (P01 CA55791, P01CA055791, R01-CA45767)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- photodynamic therapy, transferrin receptor, 5-aminolevulinic acid, protoporphyrin IX, photosensitizer accumulation, intracellular iron, lymphocyte activation, cutaneous T-cell lymphoma, Sézary syndrome, T cells, iron absorption, immunomodulation
- MeSH terms
- Aminolevulinic Acid, Cells, Cultured, Heme, Humans, Lymphocyte Activation, Lymphocytes, Mitogens, Photochemotherapy, Protoporphyrins, Receptors, Transferrin, Reference Values, Sezary Syndrome, Skin Neoplasms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
