English Version
Major conceptual and technical advances in immunology over the past 25 years have led to a new understanding of cellular and molecular interplays between the immune system and a tumor. This review deals with important new concepts in antitumor immunity and their application to immunotherapy.
Tumor Antigens
Identification
The immune system can respond to cancer cells in two ways: by reacting against tumor-specific antigens (molecules that are unique to cancer cells) or against tumor-associated antigens (molecules that are expressed differently by cancer cells and normal cells). Immunity to carcinogen-induced tumors in mice is directed against the products of unique mutations of normal cellular genes. These mutant proteins are tumor-specific antigens. Tumors caused by viruses display viral antigens that serve as tumor antigens. Examples are the products of the E6 and E7 genes of the human papillomavirus, the causative agent of cervical carcinoma, and EBNA-1, the Epstein–Barr virus nuclear antigen expressed by Burkitt’s lymphoma and nasopharyngeal-carcinoma cells.
Whether tumors of unknown cause — which account for most human tumors — express antigens that the immune system can recognize remained in doubt until the development of methods for detecting and isolating them. The advent of hybridoma technology led to the development of monoclonal antibodies from mice that were immunized with human tumors. Monoclonal antibodies that reacted specifically with tumor cells were then used to characterize putative human tumor antigens. Nevertheless, there were doubts that the tumor-specific antigens that mouse monoclonal antibodies could detect would be recognized by the human immune system.
The development of methods to propagate human T cells, and in particular tumor-specific T cells from patients with cancer, led to an important breakthrough: the identification of MAGE-1, a melanoma-specific antigen that stimulates human T cells in vitro. With antigen-specific T cells as a reagent, it was possible to clone the MAGE-1 gene. The MAGE-1 studies showed that the human immune system can respond to tumor antigens, and the findings stimulated a productive effort to discover tumor antigens. The result is a long and still-growing list of antigens from a variety of tumors that could serve as targets for treatment.
Journals for full download on the link below
Identification
The immune system can respond to cancer cells in two ways: by reacting against tumor-specific antigens (molecules that are unique to cancer cells) or against tumor-associated antigens (molecules that are expressed differently by cancer cells and normal cells). Immunity to carcinogen-induced tumors in mice is directed against the products of unique mutations of normal cellular genes. These mutant proteins are tumor-specific antigens. Tumors caused by viruses display viral antigens that serve as tumor antigens. Examples are the products of the E6 and E7 genes of the human papillomavirus, the causative agent of cervical carcinoma, and EBNA-1, the Epstein–Barr virus nuclear antigen expressed by Burkitt’s lymphoma and nasopharyngeal-carcinoma cells.
Whether tumors of unknown cause — which account for most human tumors — express antigens that the immune system can recognize remained in doubt until the development of methods for detecting and isolating them. The advent of hybridoma technology led to the development of monoclonal antibodies from mice that were immunized with human tumors. Monoclonal antibodies that reacted specifically with tumor cells were then used to characterize putative human tumor antigens. Nevertheless, there were doubts that the tumor-specific antigens that mouse monoclonal antibodies could detect would be recognized by the human immune system.
The development of methods to propagate human T cells, and in particular tumor-specific T cells from patients with cancer, led to an important breakthrough: the identification of MAGE-1, a melanoma-specific antigen that stimulates human T cells in vitro. With antigen-specific T cells as a reagent, it was possible to clone the MAGE-1 gene. The MAGE-1 studies showed that the human immune system can respond to tumor antigens, and the findings stimulated a productive effort to discover tumor antigens. The result is a long and still-growing list of antigens from a variety of tumors that could serve as targets for treatment.
Journals for full download on the link below
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