Tumor Vaccines

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.