Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 278

safety and immunogenicity of HIV-1 env / rev in patients, results showed that patients
exhibited antigen-specific production of antibodies and cytokines [34,35] . In another
clinical trial for immunization of HIV patients, the DNA vaccines were well toler-
ated, with no significant local or systemic reactions [36] . In a clinical trial for malaria
DNA vaccines, three intramuscular injections of Plasmodium falciparum circum-
sporozoite construct resulted in the production of antigen-specific, CD8 cytolytic
T lymphocytes. However, DNA vaccination failed to induce detectable antigen-specific
antibodies in any subject [20] . A clinical study was undertaken to evaluate the safety
and efficacy of DNA vaccine against hepatitis B in healthy volunteers, using a gene
gun. The results of the study showed safety, immunogenicity (production of antibodies
and antigen-specific CD8 T-cells), and tolerance of the vaccine [37] . Clinical trials
focusing on the treatment of cancer and other human diseases by using immunomodu-
lation strategy are discussed briefly under individual headings.
6.3 Applications of Gene Therapy in Cancer
Gene therapy starts up with the aim of treating genetic disorders. But the majority
of gene therapy trials have been undertaken with an objective to cure cancer, as it is
responsible for most of the mortalities annually. The gene therapy clinical trials for
cancer represent a major fraction (64.6%) of total gene therapy trials all over the world
( Fig. 6.3 ) [13] . With the understanding of the genetic basis of cancer, an entirely new
approach to the treatment of cancer using gene transfer techniques has evolved. Cancer
may result from a number of factors (carcinogens) that cause DNA damage. Moreover,
these factors change the genetic framework of cells, that is, mutations in DNA-repairing
genes or the genes that regulate normal cellular functions. These mutated genes or
other downstream genes are thought to be good targets for gene therapy [38] .
Conventional cancer therapy aims to destroy the tumor while leaving the normal
host tissue as intact as possible. The problem with both surgery and radiotherapy
is tumor invasion and spread outside areas directly accessible to these treatments;
and the problem with chemotherapy is its low therapeutic ratio for many tumors and
the fact that drug resistance may rapidly develop or may even exist from the start.
Therefore, the three conventional modalities of treatment of cancer surgery, radio-
therapy, and chemotherapy are often unsuccessful in treating cancer. Gene therapy
is the emerging fourth modality for treatment of cancer. Various types of cancer are
now active targets for gene therapy clinical trials ( Table 6.3 ) [38] . In this part of the
chapter, we are going to discuss various strategies used for cancer gene therapy in
preclinical and clinical settings, with specific emphasis on prostrate cancer, breast
cancer, brain tumors, and lung cancer.
6.3.1 Prostate Cancer
Prostate cancer is the most commonly diagnosed type of male malignancy and the
second leading cause, after lung cancer, of cancer death in men in the United States.
Around 27,360 men are expected to die of prostrate cancer in the year 2009 [39] .