Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 277

6.2.1.1 Direct Transfection of APCs
In bone marrow (BM) chimera experiments, parent cells injected into F1-BM-recon-
stituted mice created a mismatch between the haplotypes of somatic cells and BM-
derived cells. Moreover, the immune response following DNA immunization was
found to be restricted to the haplotype of reconstituted BM. These data provided clear
evidence that BM-derived cells were critical in priming immune responses after DNA
vaccination [24,25] . Moreover, experiments under in vitro conditions showed that iso-
lated dendritic cells (DCs) can efficiently present antigen to T-cell lines or hybrid-
omas [26] . All these experiments suggested that small numbers of directly transected
DCs are critical for priming immune responses following DNA vaccination.

6.2.1.2 Cross-Priming
A number of experiments showed that exogenous peptide can present MHC class I
molecules under in vivo conditions [27,28] . Delivery of vaccines to non-APCs like
myocytes [29,30] and keratinocyte [31] resulted in the generation of CTL responses.
These experiments led to the concept of “cross-priming,” that is, antigens delivered
to non-APCs like muscles that express the antigenic protein. This antigenic protein is
subsequently taken up by APCs, followed by the induction of CTL.
There are a number of disease models including infectious diseases caused by
virus, bacteria and protozoa, cancer, allergic conditions, and autoimmune disorders,
in which DNA vaccines have shown promising results ( Table 6.2 ) [32,33] .

6.2.2 Clinical Trials of DNA Vaccines
The majority of ongoing human DNA vaccination trials are focused on assessing
vaccine safety and immunogenicity, and targeted for various diseases, including
HIV, cancer, influenza, hepatitis B, and malaria. In various clinical trials to assess the

Table 6.2 List of Disease Models in Which the DNA Vaccine Has Demonstrated Efficacy

Infectious Diseases Cancer Autoimmune Diseases

HIV Breast cancer Allergy

Herpes simplex Colon cancer Diabetes

Measles Prostate cancer Multiple sclerosis

Hepatitis B, C Cervical cancer

Influenza Melanoma

Bacillus burgdorferi Lymphoma

Clostridium tetani
Mycobacterium tuberculosis
Salmonella typhi
Malaria
Mycoplasma
Leishmania