Systemic distribution and tumor localization of adoptively transferred lymphocytes in mice: comparison with physiologically based pharmacokinetic model

Neoplasia : an International Journal for Oncology Research
R J MelderRakesh K Jain

Abstract

The mechanisms by which tumors are able to evade cellular immune responses are still largely unknown. It is likely, however, that the initial recruitment of lymphocytes to tumor vessels is limited by cell retention in normal tissue, which results in a low flux of these cells into the tumor vasculature. We grew MCaIV (mouse mammary carcinoma) tumors in the leg of SCID mice and injected 111In-oxine-labeled, primed T lymphocytes directed against the tumor intravenously. The systemic distribution of cells in normal organs was similar between mice injected with primed and control lymphocyte populations, except for a delayed clearance of primed lymphocytes from the lungs. Kinetics of lymphocyte localization to the tumor were identical between the primed and control lymphocyte populations. Splenectomy before the injection of primed lymphocytes increased delivery of cells to the lungs and liver after 1 hour with no significant improvement in tumor localization. Within 24 to 168 hours after injection, localization of cells in the liver of splenectomized mice was higher than in the control group. However, no significant difference in tumor localization was observed between groups. A physiologically based compartmental model of lymphocyte...Continue Reading

Citations

Jan 29, 2003·Journal of Cellular Biochemistry. Supplement·A H JacobsW D Heiss
Apr 24, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benedetta BussolatiGiovanni Camussi
Jan 10, 2019·The Journal of Pharmacology and Experimental Therapeutics·Antari KhotDhaval K Shah
Mar 21, 2002·Nature Reviews. Cancer·Ralph Weissleder
Jan 28, 2021·AIDS Research and Human Retroviruses·Aaron S Devanathan, Angela D M Kashuba
Mar 4, 2021·Journal of the Royal Society, Interface·Liam V BrownMark C Coles
Aug 23, 2002·Neoplasia : an International Journal for Oncology Research·Stuart W FriedrichRakesh K Jain

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