Another approach is to actually develop
vaccines that you can immunize against tumors.
These could be prophylactic vaccines
against virus-associated tumors.
And there are already a
number of examples of those.
Liver cancer is linked to Hepatitis
B virus, so immunizing against
Hepatitis B virus should reduce the level of liver cancer.
Cervical cancer is associated with human papilloma viruses and
the gardasil vaccine which consists of HPV 6, 11, 16 and 18, and
cervarix which consists of just two
strains - 16 and 18, is used to
immunize young females against the
development of cervical cancer.
Of course very often one may need to treat a
patient that has already developed a tumor.
For tumor antigens, in most cases the aim is primarily
to induce specific cytotoxic T-cell responses.
But sometimes antibody
may also be desirable.
The vaccine provenge, which is a prostate cancer vaccine
uses the patient’s own cells to develop a vaccine.
Tumor vaccines can target
dendritic cells in vivo.
The tumor antigen is conjugated to an antibody
against a dendritic cell surface molecule.
For example, DEC205.
So the aim here is that you have a tumor antigen and you use
the antibody to take that tumor antigen to the dendritic cells.
And then the tumor antigen will be taken up by the
dendritic cells, processed and presented to T-cells.
Monocytes or CD34+ precursors can be loaded with
tumor antigens and differentiated into dendritic
cells using cytokines, such as granulocyte macrophage
colony stimulating factor and interleukin-4.
So you take patient cells, incubate them with the antigen,
make the dendritic cells develop from the blood monocytes.
And then re-infuse the dendritic
cells back into the patient.
Provenge or Sipuleucel-T is approved by the
FDA for the treatment of asymptomatic or
minimally symptomatic metastatic castrate-resistant
(hormone-refractory) prostate cancer.
In this strategy on day one, the patient undergoes
leukapheresis to isolate precursors of dendritic cells.
Prostatic acid phosphatase linked to the cytokine
GM-CSF is incubated with these isolated blood cells.
And over the course of two or three days, the GM-CSF causes
differentiation of these blood leukocytes into dendritic cells.
And the prostate acid phosphatase tumor antigen gets delivered
via these dendritic cells, when infused back into the patient.
T-cells within the patient will become activated,
that are specific for this tumor antigen.
The whole process is repeated
at weeks two and four.