Tumor infiltrating lymphocytes

IL-2+ LAK cell or tumor infiltrating lymphocyte tumor destmction rodent and human... 

To date, cellular and gene therapy products submitted to FDA have included clinical studies indicated for bone marrow marking, cancer, cystic fibrosis, AIDS, and inborn errors of metabolism and infectious diseases. Of the current active INDs approximately 78% have been sponsored by individual investigators or academic institutions and 22% have also been industry sponsored. In addition to the variety of clinical indications the cell types have also been varied. Examples include tumor infiltrating lymphocytes (TIL) and lymphocyte activated killer (LAK) cells, selected cells from bone marrow and peripheral blood lymphocytes, for example, stem cells, myoblasts, tumor cells and encapsulated cells (e.g., islet cells and adrenal chromaffin cells). 

Filgueira L, Zuber M, Juretic A, et al. Differential effects of interleukin-2 and CD3 triggering on cytokine gene transcription and secretion in cultured tumor infiltrating lymphocytes. Cell Immunol 1993 150 205. 

Kasid, A., Morecki, S., Aebersold, P, et al. (1990). Human gene transfer characterization of human tumor-infiltrating lymphocytes as vehicles for retroviral-mediated gene transfer in man. Proc. Natl. Acad. Sci. U.S.A., 87, 473 -77. 

Robbins PF, El-Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA (1996) A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 183(3) 1185—1192... 

Infusion of tumor-infiltrating lymphocytes (TIL) isolated from tumor samples and expanded in vitro with rIL2 resulted in a more efficient tumor reduction in animal models [19] and showed activity in clinical studies [20], A significant impediment to generating therapeutic TILs resides in the inherent... 

Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor infiltrating lymphocytes. Science 1986 233 1318-21. 

Kradin FL, Lazarus DS, Dubinett SM, et al. Tumor infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Lancet 1989 2 577-80. 

Fitzpatrick-McElligott, S. (1992). Gene transfer to tumor-infiltrating lymphocytes and other mammalian cells by microprojectile bombardment. Bio/Technology 10,1036 1040. 

In early trials, aldesleukin was given with lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes. However, later data showed that the addition of LAK cells does not improve the therapeutic response in renal cell carcinoma and can produce more pulmonary toxicity and hypotension (1). Compared with aldesleukin or interferon alfa alone, the combination of aldesleukin plus interferon alfa produces a significantly longer event-free survival without effect on the overall survival, but induces substantial toxicity with severe and resistant hypotension (3). The optimal safe and effective dose and schedule of administration of aldesleukin is not yet well defined, and a variety of regimens have been tested, with doses of 600 000 units/kg by intermittent bolus intravenous infusion or 18 106 units/m by continuous subcutaneous or intravenous infusion. 

Much attention has been paid to the role of CD8 T cells in the immunotherapy of cancer due to the cytotoxic property of these cells, and a large number of MHC class I-restricted tumor antigens have been identified using tumor-reactive CD8 T cells from patients peripheral blood mononuclear cells (PBMCs) or tumor-infiltrating lymphocytes (TILs) [283,289,290]. 

Coventry BJ, Weeks SC, Heckford SE, et al. Lack of IL-2 cytokine expression despite 11-2 messenger RNA transcription in tumor-infiltrating lymphocytes in primary human breast carcinoma selective expression of early activation markers. J Immunol 1996 156 3486-92. 

In recent years, interest has focused on the role of cell-mediated immune response in melanoma. Specific cell-mediated responses may play a role in tumor regression, but the role of specific cells such as cytotoxic T lymphocytes (CTLs) is not fully understood. Tumor-infiltrating lymphocytes (TILs) have been shown in vivo and in vitro to possess antitumor reactivity. TILs contain a large number of mature tumor-specific lymphocytes and have been a target for manipulation in immunotherapeutic approaches for melanoma. 

Presence of tumor-infiltrating lymphocytes (correlated with increased survival)... 

LDI low-dose interferon MAA melanoma-associated antigen NSAID nonsteroidalanti-inflammatory drug SPF sun protection factor TAA tumor-associated antigen TIL tumor-infiltrating lymphocyte UVA ultraviolet A UVB ultraviolet B... 

Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report [see comments]. N Engl J Med 1988 319(25) 1676-1680. 

Signore A, Annovazzi A, Barone R et al (2004) c-interleukin-2 scintigraphy as a potential tool for evaluating tumor-infiltrating lymphocytes in melanoma lesions a validation study. J Nucl Med 45 1647-1652... 

Gene Therapy of Patients with Advanced Cancer Using Tumor Infiltration Lymphocytes Transduced with the Gene Coding for Tnmor Necrosis Factor... 

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