Adoptive cell transfer

Powell, D. J., Jr., M. E. Dudley, P. F. Robbins, and S. A. Rosenberg. 2005. Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy. Blood 105 241-250. 

Dudley ME et al. Adoptive cell transfer therapy following non-myeloablative but lym-phodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005 23 2346-2357. 

Liu S, Riley J, Rosenberg S, Parkhurst M. Comparison of common gamma-chain cytokines, interleukin-2, interleukin-7, and interleukin-15 for the in vitro generation of human tumor-reactive T lymphocytes for adoptive cell transfer therapy. J Immunother 2006 29 284-293. 

Finally, mention should be made of a promising new class of cancer immunotherapy undergoing early-stage testing. In this therapy, called adoptive cell transfer (ACT), tumor-reactive lymphocytes are harvested from a patient with melanoma, activated and expanded ex vivo, and then infused back into the patient. The result, in many patients, is the production of lymphocytes with increased tumor-fighting capacity. Research is ongoing to optimize clinical results from this type of treatment. 

Dillman RO, Church C, Barth NM, Oldham RK, Wiemann MC (1997) Long-term survival after continuous infusion interleukin-2 Cancer Biother Radiopharm 12 243-248 Dudley ME, Rosenberg SA (2007) Adoptive cell transfer therapy. Semin Oncol 34 524-531... 

A broad and vigorons T cell response generally accompanies elimination of HBV as well as HCV infection. By contrast, patients with chronic hepatitis B or C tend to have late, transient, or narrow T cell responses. In a long-term follow-up of HBV-infected patients receiving HPC transplants from HBV-immune individuals, 20 of 31 recipients cleared their HBV infection (Hui et al. 2005). In principle, these results encourage the development of adoptive T cell transfer strategies for the treatment of chronic viral hepatitis. However, it is still controversial whether induction of an efficient T cell response is the cause or the consequence of viral clearance. Furthermore, T cell responses do not only contribute to virus control but also to disease pathology (Rehermann and Nascimbeni 2005). 

Here, we describe how to quantitatively and qualitatively describe neutrophil migratory behavior in a defined peripheral tissue site in vivo using multiple complementary methodologies, including immunohistochemistry (IHC), flow cytometry (FCM), enzymatic activity, and MP-IVM in live mice. We also describe the methods of neutrophil isolation from mouse BM, neutrophil labeling with with cell tracker dyes, adoptive neutrophil transfer, and mixed BMC approaches to study the role of chemoattractant receptors in neutrophil recruitment into the joint in a model of inflammatory arthritis. 

The in vivo relevance and biological importance of in vitro observations about mast cell function, as well as the contributions of mast cells towards the expression of particular biological responses (such as various models of anaphylaxis) in vivo, can be assessed using c-kit mutant mice (e.g., WBB6Fi-FCit or mice) that virtually lack mast cell populations. Mice with mutations of c-kit [6,11] or mutations that affect KIT expression [12-14] have other abnormalities of phenotype besides a mast cell deficiency. However, the mast cell deficiency of these mice can be selectively repaired by the adoptive transfer of genetically compatible, in vitro-derived... 

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