Tumor Antigens Recognized by T Lymphocytes

Abstract

Transplantation experiments have demonstrated that most mouse tumors express antigens that can constitute targets for rejection responses mediated by syngeneic T lymphocytes. For human tumors, autologous cultures mixing tumor cells and blood lymphocytes or tumor-infiltrating lymphocytes have produced CD8+ and CD4+ cytolytic T cell (CTL) clones that recognize tumor cells specifically. Attempts to identify the target antigens by biochemical fractionation of tumor cells up to now have failed, with the important exception of the identification of underglycosylated mucins present on breast and pancreatic carcinomas. Gene transfection approaches have proved more successful. A gene family named MAGE codes for antigens recognized by autologous CTL on a melanoma tumor. These genes are not expressed in normal tissues except for testis. They are expressed in many tumors of several histological types. Differentiation antigens coded by genes such as tyrosinase are also recognized on human melanoma by autologous CTL. The identification of human tumor rejection antigens opens new possibilities for systematic approaches to the specific immune therapy of cancer.

GM-CSF-secreting melanoma vaccines

“…Although humoral and cellular responses to malignant melanoma were first demonstrated more than 20 years ago (Old, 1981), the crafting of genetic and biochemical strategies to identify the molecular targets of these responses dramatically advanced the field of cancer immunology (Boon et al, 1994). These cloning strategies uncovered a surprisingly diverse array of gene products that stimulate immune recognition (Boon and van der Bruggen, 1996;Old and Chen, 1998).…”

Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure

“…This view is supported by a number of experimental (1) and clinical data (2). Currently, most attempts at cancer immunotherapy involve the generation of CTLs against tumor-associated antigens (TAA).…”

Human Tumor Antigen-Specific Helper and Regulatory T Cells Share Common Epitope Specificity but Exhibit Distinct T Cell Repertoire

“…T here is ample evidence that melanoma cells express tumor Ags (TAs) that are recognized by T cells isolated from peripheral blood or tumor-infiltrating lymphocytes (TILs) of patients with melanoma (1). However, the presence of TAspecific T cells, even in large numbers, is not consistently correlated with a positive clinical outcome (2).…”