00:01
Another approach is to actually develop
vaccines that you can immunize against tumors.
00:09
These could be prophylactic vaccines
against virus-associated tumors.
00:14
And there are already a
number of examples of those.
00:18
Liver cancer is linked to Hepatitis
B virus, so immunizing against
Hepatitis B virus should reduce the level of liver cancer.
00:28
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.
00:51
Of course very often one may need to treat a
patient that has already developed a tumor.
00:57
For tumor antigens, in most cases the aim is primarily
to induce specific cytotoxic T-cell responses.
01:04
But sometimes antibody
may also be desirable.
01:08
The vaccine provenge, which is a prostate cancer vaccine
uses the patient’s own cells to develop a vaccine.
01:17
Tumor vaccines can target
dendritic cells in vivo.
01:22
The tumor antigen is conjugated to an antibody
against a dendritic cell surface molecule.
01:28
For example, DEC205.
01:30
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.
01:39
And then the tumor antigen will be taken up by the
dendritic cells, processed and presented to T-cells.
01:48
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.
02:05
So you take patient cells, incubate them with the antigen,
make the dendritic cells develop from the blood monocytes.
02:15
And then re-infuse the dendritic
cells back into the patient.
02:20
Provenge or Sipuleucel-T is approved by the
FDA for the treatment of asymptomatic or
minimally symptomatic metastatic castrate-resistant
(hormone-refractory) prostate cancer.
02:36
In this strategy on day one, the patient undergoes
leukapheresis to isolate precursors of dendritic cells.
02:49
Prostatic acid phosphatase linked to the cytokine
GM-CSF is incubated with these isolated blood cells.
03:01
And over the course of two or three days, the GM-CSF causes
differentiation of these blood leukocytes into dendritic cells.
03:11
And the prostate acid phosphatase tumor antigen gets delivered
via these dendritic cells, when infused back into the patient.
03:24
T-cells within the patient will become activated,
that are specific for this tumor antigen.
03:30
The whole process is repeated
at weeks two and four.