UroToday - AUA 2008 - State-of-the-Art Lecture: Immune-Based Approaches to Prostate Cancer

[Guest guest]

Wednesday, 21 May 2008

ORLANDO, FL

(UroToday.com) - Dr. Drake, a medical oncologist from s Hopkins discussed

use of the immune system to combat CaP. ProVenge and GVAX immunotherapy were

discussed. Both have reached phase III clinical trials. The immune system uses

the CD8 killer T cell to respond to cancer. There are 1010 possible receptors

to target immune therapies. Tumors escape the immune system by mutation and

inducing immune checkpoints. The host expresses circulating cytokines that are

immunosuppressive and poor expression and function of dendritic cells also

occurs. CD8 cells are activated by activated dendritic cells to target cancer.

For

treatment with ProVenge, patient’s white blood cells are harvested,

exposed to an activating cassette and GM-CSF, cryopreserved and then re-infused

into the patient. A phase III trial randomized hormone-refractory prostate

cancer patients (HRPC) patients to 3 rounds of ProVenge or placebo. The

secondary endpoint of overall survival was met. The FDA deemed the approach

approvable, but wanted more survival data. The new survival data is expected

later this year.

GVAX is a

cell-based immunotherapy using CM-CSF stimulation of immature dendritic cells.

Immune monitoring is difficult in this setting. A phase II trial randomized

patients to docetaxel or GVAX. The primary endpoint is overall survival. The

results are expected late in 2009. A combination with chemotherapy is also

under evaluation. He showed data that castration combined with immunotherapy

holds promise and will be under study in an ECOG trial.

He discussed

immune checkpoints that are “brakes” to holding the immune response

back. He provided an example of how immunotherapy in CaP cells is affected by

PD-1, an immune checkpoint.

Presented

by Drake, MD, at the Annual

Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County

Convention Center - Orlando, Florida, USA.

http://tinyurl.com/3nr5rf