Genetic approaches to adoptive cellular therapy of malignancy.
The rapid strides made in recombinant gene technology have been the impetus for equally dramatic developments in our understanding of various aspects of cancer biology. These areas include genetic events leading to carcinogenesis, growth factors, cellular proliferation, differentiation, apoptosis, and metastasis. Novel therapeutic approaches that take advantage of this new knowledge involve biological alteration of the host target cell at a genetic level. Many of these approaches are discussed in greater detail in other sections of this issue. This article focuses on genetic approaches to the adoptive immunotherapy of malignancy. This form of cellular therapy refers to the infusion of tumor reactive immune cells to mediate regression of established tumor. This review is divided into several areas, each one involving different methods of genetic manipulation to generate immune cells for subsequent adoptive transfer and include: (1) the use of gene-modified tumors to serve as immunogens to generate antitumor T cells, (2) genetic manipulation of effector cells to enhance antitumor reactivity; and (3) genetic construction of immunocompetent effector cells from naive cells.
Arca
M J
MJ
Division of Surgical Oncology, University of Michigan, Ann Arbor, USA.
Mulé
J J
JJ
Chang
A E
AE
D000818:Animals; D016207:Cytokines / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014162:Transfection
D016207:Cytokines