Targeted T Cells for PCa are here, let the Clinical Trials begin...

[Attitude67]

It started: 

A few years ago In a cancer treatment breakthrough 20 years in the making, researchers from the University of Pennsylvania's Abramson Cancer Center and Perelman School of Medicine were able to show sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells. The protocol, which involves removing patients' cells and modifying them in a vaccine production facility, then infusing the new cells back into the patient's body following chemotherapy, provided a tumor-attack roadmap for the treatment of this and other cancers. The findings were the first demonstration of the use of gene transfer therapy to create "serial killer" T cells aimed at cancerous tumors.

It's here:

Adoptive Transfer of Autologous T Cells Targeted to Prostate-Specific Membrane Antigen for the Treatment of Metastatic Castration-Resistant Prostate Cancer (CMPC)

Where:

Memorial Sloan Kettering: mskcc.org/

Purpose:

This phase I study will evaluate the safety and effectiveness of different doses of a patient’s own immune cells (T cells) which have been changed to help recognize and destroy his prostate cancer cells by targeting a protein called prostate-specific membrane antigen. The T cells are removed from the patient’s blood, modified with a gene in the laboratory so they are better able to recognize and kill prostate cancer cells, and then returned to the patient’s body. This gene is inserted into the T cells using a weakened virus. /

It is hoped that this approach will help each patient’s own T cells recognize his prostate cancer cells and possibly kill them.

Eligibility for the Clincal Trials:

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

Patients must have metastatic prostate cancer that has not yet been treated with chemotherapy. Patients may have had hormonal therapy.

Patients must have rising PSA levels and a serum testosterone level under 50 ng/mL.

Patients must be age 18 or older.

For more information about this study and to inquire about eligibility, please contact Dr. Susan F. Slovin at 646-422-4470 or Dr. Howard Scher at 646-422-4330.

[JoelT]

It is interesting because Provenge is similar, but the target is PAP a protein that appears on the cancer cell.  There is also, in phase 3 trials, another similar sensitizing  of T cells call Prostvac (the target instead is the protein PSMA like the trial you mentioned).  I don't believe that the Prostvac treatment is using a genetic manipulation.

Joel

[Attitude67 in reply to JoelT]

Vacines use some of the same or similar targets however this approach employs an entirely new technology called "Gene Transfer Therapy."

After removing the patients' cells, they are reprogrammed to attack tumor cells by genetically modifying them using a lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to the target proteins. Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express the target. All of the other cells in the patient that do not express the target are ignored by the modified T cells, which limits the side effects typically experienced during standard therapies. A signaling molecule is inserted into the part of the CAR that resides inside the cell. When it binds to The target it initiates cancer-cell death, and also tells the cell to produce cytokines that trigger other T cells to multiply -- building a bigger and bigger army until all the target cells in the tumor are destroyed. In treating Chilhood Leukemia researchers at the University of Pennsylvania saw at least a 1000-fold increase in the number of modified T cells in each of their patients. In addition to an extensive capacity for self-replication, the infused T cells are serial killers. On average, each infused T cell leads to the killing of thousands of tumor cells. Overall the expectation is that each treatment may be capable destroying at least two pounds of tumor in each patient. The danger is that the patient will begin experiencing chills, nausea, and increasing fever, among other symptoms. An enormous increase in the number of T cells in the patients blood can lead to tumor lysis syndrome, which occurs when a large number of cancer cells die all at once.