Abstract and Introduction
Abstract
We have seen a surge in the use of immunotherapy for the treatment of cancer. Biological response modifiers can act passively by enhancing the immunologic response to tumor cells or actively by altering the differentiation/growth of tumor cells. Active immunotherapy with cytokines such as interferons (IFNs) and interleukins (IL-2) is a form of nonspecific active immune stimulation. The use of IL-2 has recently been approved by the United States Food and Drug Administration (FDA) for the treatment of renal cell carcinoma and metastatic colorectal cancer.
Considerable success has been achieved with the use of immunotherapy, especially in the area of passive immunotherapy using monoclonal antibodies -- in particular, radiolabeled monoclonal antibodies. In addition to the various monoclonal antibodies that have been used in clinical trials, other strategies such as the use of antiangiogenic agents and matrix metalloprotease inhibitors (MMPIs) have also met with some success. Recently, the FDA approved bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, for the treatment of metastatic melanoma.
This review also sheds light on the various angiogenesis inhibitors in clinical trials, the increasing use of thalidomide in cancer, and the upcoming potential cancer vaccines designed to activate cell-mediated immune responses against tumor antigens.
Introduction
Over the last few years, immunotherapy has been widely investigated for the treatment of cancer. The goal of immunotherapy is to manipulate the host tumor interaction in favor of the host. Cancer cells express a wide profile of different proteins that act as antigens. Some of these antigenic proteins may be a result of oncogenic transformation and are relatively specific to cancer cells. These tumor-associated antigens are delivered to the immune system by antigen-presenting cells (APCs) through major histocompatibility complex (MHC) class I or class II pathways. In the class I pathway, the phagocytosed tumor cells are processed by proteasomes and converted to short peptide fragments, which are then presented on class I MHC molecules. These are recognized by CD8+ cytotoxic lymphocytes, which have direct cytotoxic effects leading to tumor cell lysis. In the class II pathway, the secreted products from tumor cells enter the APCs, which are then processed and presented to MHC class II molecules. These processed antigens are recognized by CD4+ helper lymphocytes, which enhance the CD8+ cytotoxic responses as well as the humoral response to surface antigens present on tumor cells. Thus, T-helper lymphocytes have been shown to activate APCs along with sustaining the immune response via cytokines.
Biological response modifiers can act passively by enhancing the immunologic response to tumor cells or actively by altering the differentiation/growth of tumor cells. Active immunotherapy with cytokines such as interferons (IFNs) and interleukins (IL-2) is a form of nonspecific active immune stimulation. The IFNs have been tested as therapies for many hematologic and solid neoplasms and have demonstrated therapeutic benefits in various cancers. Moreover, IL-2 has already gained FDA approval for the treatment of renal cell carcinoma and metastatic melanoma. Success has been achieved in the area of immunotherapy, especially in the area of passive immunotherapy using monoclonal antibodies. Other strategies, such as the use of antiangiogenic agents, matrix metalloprotease inhibitors(MMPIs), tyrosine kinase inhibitors (TKIs), and tumor vaccines, have also been met with some success.
One of the major adverse effects of cancer chemotherapy is immunosuppression, which leads to many opportunistic infections, so hematopoietic factors (such as colony stimulating factor [CSF]) have been utilized to increase the immune response. Hematopoietic agents such as granulocyte macrophage colony-stimulating factor (GM-CSF; sargramostim) and granulocyte colony-stimulating factor (G-CSF; filgrastim) have been used to increase immunity. Biological response modifiers are basically used alone or as adjuvants to cancer chemotherapeutic agents.
© 2006
Medscape
Cite this: Biological Response Modifiers in Cancer - Medscape - Nov 14, 2006.
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