Identification of Tumor Antigens

The identification of many antigens expressed by naturally occurring human tumors represents a major advance in the field of tumor immunology. Various biochemical and molecular genetic approaches have been used to identify these antigens. For tumor antigens recognized by CD8+ cytotoxic T lymphocytes (CTLs), investigators have established cloned lines of tumor-reactive CTLs from cancer patients and used these as probes to specifically identify the relevant peptide antigens or the genes encoding the peptides. For example, many cloned CTL lines specific for melanomas have been generated from the T cells of patients. Melanomas, which are malignant tumors of melanocytes, are often readily accessible, surgically resectable tumors that may be grown in tissue culture. The T cells can be isolated from peripheral blood, lymph nodes draining the tumor, or directly from tumor tissue removed from patients. These T cells can be stimulated to grow in vitro by coculture with the tumor cells, and individual clones can be isolated. Because the T cells and the tumor are from the same individual, the major his-tocompatibility complex (MHC) restriction of the T cells matches the MHC alleles expressed by the tumor. These tumor antigen-specific CTL clones have been used to detect responses to tumor-derived peptides or responses to proteins made by complementary DNA (cDNA) libraries of the tumor (Fig. 17-3). Such approaches were first used to identify human melanoma antigens that stimulated CTL responses in patients with melanoma. The same methods have been used to identify antigens that are recognized by CD4+ helper cells, in which case the probes are helper T cell clones derived from patients' CD4+ T cells.

A successful method for identification of tumor antigens that have stimulated humoral immune responses in tumor patients is called the serologic analysis of recombinant cDNA expression (SEREX). In this method, expression libraries of cDNA derived from a patient's tumor RNA are transfected into a cell line, and assays are performed to detect binding of the cancer patient's serum immunoglobulins to the transfected cells. In this way, gene sequences for targeted proteins are obtained, and the encoded proteins that have stimulated antibody responses in the patient are identified.

In the following section, we describe the main classes of tumor antigens (Table 17-1). We will include tumor antigens known to induce immune responses in humans

Generation of tumor-specific CTL clones

Purify mononuclear cells from tumor site

Purify mononuclear cells from tumor site

Surgically resect tumor

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