Immunotherapy for Infectious Diseases

From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
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Immunotherapy for Virus-Associated Malignancies
INTRODUCTION
Uluhan Sili, Helen Heslop, and Cliona M. Rooney
Estimates of the fraction of human malignancies that are associated with viral infections
range from 10% to 20% (1). Among viruses and their associated cancers are
Epstein-Barr virus (EBV), which is associated with many different malignant diseases
including lymphoproliferative disease (LPD) in immunosuppressed patients, Hodgkin’s
disease, Burkitt’s lymphoma and nasopharyngeal carcinoma; human papillomaviruses
(HPV) types 16 and 18 with cervical cancer; hepatitis B (HBV) and hepatitis C viruses
with hepatocellular carcinoma; human T-cell leukemia virus-1 with adult T-cell lymphoma;
and human herpes virus-8 with Kaposi’s sarcoma in patients with AIDS.
Much of the evidence for the association of viruses with human cancer comes from
epidemiologic data (2). EBV and HPV have a high prevalence in most populations, but
only a small proportion of infected persons develops a virus-associated cancer. The
period of latency between primary infection and tumor outgrowth underscores the multifactorial
origins of human tumors. Further evidence for the association of viruses with
cancer comes from the detection of viral DNA in tumor tissue, the ability of viruses to
transform cells in vitro, and the expression of viral proteins with oncogenic potential
or the ability to inactivate tumor suppressor genes. Regardless of their precise role in
oncogenesis, viral tumor-associated antigens can serve as targets for immunotherapy.
The cytotoxic T-lymphocyte (CTL) arm of the cellular immune response is thought to
be the most important defense against tumors and virus-infected cells. In this chapter,
we discuss the use of EBV-specific CTLs as immunotherapy for EBV-associated malignancies.
Other tumor-associated viruses are covered only briefly.
GENERATION OF CELL-MEDIATED IMMUNE RESPONSES
The design of successful immunologic strategies to treat human virus-associated
malignancies requires an understanding of the effector processes that control viral
infection and the mechanisms viruses use to evade such responses. Immune responses
against viruses are mediated by nonspecific effector cells, such as natural killers and
macrophages, and antigen-specific T- and B-lymphocytes.
Antibody-mediated humoral immunity effectively neutralizes extracellular virus.
Once inside the cell, viruses are likely to be protected from antibody and therefore