Interferons: Cellular and Molecular Biology of Their Actions

Interferons (IFNs) are secretory proteins produced by virus-infected cells. The name interferon refers to their ability to interfere with viral replication. However, IFNs induce several pleiotropic responses, including antiviral, antitumor, immunomodulatory, antiparasitic, and antiproliferative activities. In addition to viral infection, double-stranded RNA (dsRNA), fungal cell wall products, and other cytokines also induce the production of IFNs. dsRNA may be a physiologically relevant regulator of IFN synthesis because it is thought to be an intermediate product of viral infection.

Graft versus Leukemia and Graft versus Tumor Activity

Since the 1950s there has been experimental and subsequently clinical evidence for an effect of allogeneic hematopoetic cells against leukemias (graft versus leukemia, GvL) and, more recently, solid tumors (graft versus tumor, GvT). The success of donor leukocyte infusions (DLI) as a therapy for relapsed chronic myelogenous leukemia (CML) after bone marrow transplant (BMT) is the ultimate proof of the antitumor activity of allogeneic cells.

DNA-Based Cancer Vaccines

Plasmid DNA vaccines represent a relatively new approach to immunization against antigens present on cancer cells. DNA vaccines are relatively simple to prepare and administer and present multiple epitopes within the complete coding sequence of an antigen. Immunostimulatory sequences naturally occurring in bacterial DNA may add to the ability of DNA vaccines to induce both antibody and T-cell responses. The results of experiments using mouse melanoma models have suggested that DNA immunization is a promising new approach to cancer vaccine therapy.


DNA Damage, DNA Repair, and Mutagenesis

DNA damage consists of (a) formation of carcinogen-DNA adducts and other chemical modifications of DNA bases and (b) alterations in DNA ultrastructure (DNA strand cross-links/DNA strand breaks/chromatid exchanges/chromosomal loss). DNA damage can be induced by endogenous processes and by exogenous chemical and physical agents. A potential consequence of DNA damage is mutagenesis, i.e., a permanent alteration in DNA structure that produces miscopying of information during DNA replication and yields abnormal gene products (proteins).

Cell-Mediated Immunity to Cancer

Cell-mediated immunity to cancer principally relies on the specificity of the interaction between T cells and tumor antigens presented by tumors and antigen-presenting cells (APC), although other types of cells may be the ultimate effectors. Many tumor antigens have been discovered in recent years. The immune system has been shown to recognize antigens that are shared between cancer and normal tissue, as well as those that are created by genetic alterations in the tumor.

Carbohydrate-Based Vaccines

Carbohydrate antoantigens have proven to be suitable targets for immune recognition and attack against cancer cells, because of their abundance at the cell surface and their unexpected immunogenicity.       
Carbohydrates play key roles in intracellular interactions as targets for selectins and adhesins, which may be crucial, not discretionary, to tumor cell survival and the metastatic process. Passively administered and vaccine-induced antibodies in preclinical models are capable of interfering with these processes directly, inducing complement-mediated inflammation and lysis and mediating opsonization, inflammation, and tumor cell death by other Fc-mediated mechanisms.

Cancer Vaccines: Peptideand Protein-Based Vaccines

Methods developed over the last several years have allowed tumor antigens that are recognized by MHC class I- and class II-restricted T cells to be readily identified. The screening of patient sera against tumor cell cDNA expression libraries has also resulted in the identification of a large number of antigens, some of which were also found to be recognized by tumor-reactive T cells. These antigens, as well as proteins that appear to be overexpressed in tumors, represent targets that can potentially be used for the development of cancer vaccines.      

Cancer Vaccines: Gene Therapy and Dendritic Cell-Based Vaccines


Immunologists have long tried to exploit the immune system to control human disease, in many cases with great success. The prevention of viral diseases by immunizations that stimulate durable antibody responses is a cardinal example. Cancer and certain other infections have proven more elusive, however. Among the myriad reasons for this are that most tumor antigens (Ags) are self or differentiation Ags to which the immune system is not responsive, the tumor microenvironment itself may be inhibitory, and tumor cells lack the other surface molecules required for immunogenicity.  

Antibody-Toxin and Growth Factor-Toxin Fusion Proteins

The goal of cancer treatment is the elimination of tumor cells while inflicting the least amount of harm to normal cells. Because approximately half of all cancers are not cured using conventional therapies, new strategies are needed. One emerging therapeutic approach is the targeted delivery of highly toxic substances.


Anti-idiotypic Antibody Vaccines

Anti-idiotypic antibodies bind to unique regions on other antibody molecules. One of the central hypotheses of modern immunology is that the immune system is regulated through a network of antibody-anti-idiotypic antibody interactions. One consequence of this theory is the idea that a specific B- or T-cell clone can be specifically activated by the appropriate anti-idiotypic antibody. In this way, antiidiotypic antibodies may be used as vaccines to induce active immunity against a foreign antigen.