Designer T cells reduced PSA in metastatic prostate cancer

AACR 100th Annual Meeting

T cells that have been modified to target prostate-specific membrane antigen reduced PSA values after one month of treatment, according to the results of a small phase-1 study.

“T cells are the perfect killing machine,” said Richard Junghans, MD, PhD, associate professor of surgery and medicine at Boston University School of Medicine. However, instead of killing virus-infected cells, Junghans and colleagues modified T cells to attack the PSMA that is present in men with metastatic prostate cancer.

“By grafting the antibody onto the zeta chain of the T cell receptor we are able to redirect these T cells to attack the cancer based on the expression of PSMA,” said Junghans at the AACR 100th Annual Meeting in Denver.

In the study, a “hematologic space” in the body is first created by chemotherapy in which these designer T cells expand up to 100-fold in number after infusion to increase their potency, according to Junghans.

The two patients currently enrolled in the study are being treated at 10⁹T cells. T cells are infused on day zero and low-dose interleukin-2 is administered for 28 days after infusion.

“The PSA, which is our tumor marker for prostate cancer, went down 50% in one patient and 75% in the second patient,” Junghans said. “Designer T cells propose a 'brave new world' for cancer therapies because these are not inert chemicals or molecules; they are living cells engineered to seek and destroy.” – by Leah Lawrence

For more information:

Junghans RP. #5662. Presented at: AACR 100th Annual Meeting; April 18-22, 2009; Denver.

Richard Junghans, MD, comments on a phase-1 trial of anti-PSMA designer T cells in prostate cancer:

Richard Junghans, MD, PhD
Richard Junghans

We developed this [approach] through the usual preclinical experimentation and testing, making sure that our antibody didn’t cross-react with normal tissues. It was proposed to the FDA and we got FDA approval to do experiments in human beings. We then had the vector made as clinical grade. The vector is a special type of virus used to carry DNA into the T cells to create their new receptor that makes them 'designer' T cells.

Then we began our phase-1 study. So far, we have treated two patients but are trying to treat 15 in total. If data are encouraging in terms of response rates, then we will go on to do a larger phase-2 study to further examine response rates. Because [metastatic prostate cancer] is incurable and it is very well known that there are limitations on survival expectations after failing hormone therapy and chemotherapy, any cure in this patient group would almost be an automatic license.

The question is how we would make it accessible to a lot of patients because the method is very technology driven. Imagine treating 1,000 patients in a month. In that case we would have to come up with a different model for distribution. One group of people that has experience with working with blood cells and keeping them sterile is the Red Cross and blood banks throughout the country. What we would need to do is invent a way to do a 'shake and bake' type of thing where a patient donates a unit of blood, it gets processed to lymphocytes and we then add our vector to it. Those cells would be modified and then maybe growth factor is added and then you store it. It is then sent back to a patient’s oncology clinic and infused.

If we are doing this right, I would expect that we would only have to treat once. There would be a sustained response in the suppression of the tumor until it’s eliminated.