A novel approach to generate host antitumor T cells: Adoptive immunotherapy by T cells maturing in xenogeneic thymus
University of Nebraska at Omaha, Omaha, Nebraska, United States Journla of Immunotherapy
(Impact Factor: 4.01).
02/2007; 30(1):83-8. DOI: 10.1097/01.cji.0000211322.45772.d4
Mouse or human T cells developing in xenogeneic porcine thymus are functional. With efficient peripheral repopulation of mouse T cells by grafting fetal pig thymus (FP THY), B6 nude mice were immunized with inactivated syngeneic melanoma, B16 cells. Splenocytes from B16-immunized FP THY-grafted B6 nude mice efficiently killed B16, but not EL4 target cells in cytotoxicity assays in vitro. Adoptive transfer of splenocytes from B16-immunizd FP THY-grafted B6 nude mice to B16-bearing B6 mice significantly prolonged recipient survival and inhibited B16 solid tumor growth when B16 cells were injected IV or SC, respectively, compared with the identical controls. Splenocytes from nonimmunized FP THY-grafted B6 nude mice failed to protect B6 mice from B16-induced mortality. The present data have demonstrated that mouse T cells maturing in xenogeneic thymus have the ability to kill syngeneic tumor cells. This study may offer a novel resource to produce host antitumor T cells for adoptive immunotherapy of tumor patients.
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ABSTRACT: Solid tumors consist of neoplastic cells, non-malignant stromal cells and migratory haematopoietic cells. Complex interactions
between the cell types in this microenvironment regulate tumor growth, progression, metastasis and angiogenesis. There is
also strong evidence that this microenvironment is inflammatory and that activation of the innate immune system plays a role
in the progression of cancer. One such inflammatory cell that has the potential to promote cancer progression is the macrophage.
There is a growing body of pre-clinical and clinical evidence associating abundance of tumor-associated macrophages (TAM)
with poor prognosis. According to Condeelis and Pollard, TAM are obligate partners for malignant cell migration, invasion
and metastases in many different cancers. These conclusions are based not only on association studies, but also on experiments
that show ablation of macrophage function, or their infiltration into experimental tumors, inhibits growth and metastases.
12/2009: pages 371-383;
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