New ‘immune checkpoint’ vaccine shows promise in treating colorectal cancer

A novel vaccine may provide a breakthrough treatment option in colorectal and other cancers.

“We [researchers] at the Peter MacCallum Cancer Centre in Melbourne, Australia, have developed a new, DNA-based vaccine, which we call TetMYB, for the treatment of MYB-overexpressing cancers such as colorectal, adenoid cystic carcinoma, and breast cancer, to name a few,” Toan Pham, MD, of the Peter MacCallum Cancer Centre, said in a media briefing in advance of the annual Digestive Disease Week^® conference.

The immunotherapy approach described by Dr. Pham involves combining the TetMYB vaccine, which boosts the immune system, and an antibody, BGB-A317, that helps enhance the effectiveness of the vaccine.

luiscar/Thinkstock

The vaccine is administered in the skin where it is taken up via the dendritic cells, which then migrate to the lymph glands where they transfer the vaccine to the cytotoxic T cells, which target and kill cancerous tissues. When these cytotoxic T cells interact with tumor cells, they often encounter countermeasures from the tumors that attempt to inactivate the immune cell by binding to the PD-1 receptor on the cytotoxic T cell. This is why the BGB-A317 antibody is so important. It will bind to the PD-1 receptor, which blocks the PD-L1/L2 ligand on the tumor cell from binding to the T cell, rendering its cytotoxic effects useless. This “immune checkpoint” allows the cytotoxic T cells to function normally, and lyse the tumor cells.

“The research we are presenting at DDW involves testing this approach in mouse models, which we had previously published. In our studies, tumors in the mice responded very well to the treatment and cancer was cured in about half of them,” stated Dr. Pham.

The study is really composed of two smaller studies that looked at colonic adenoma, induced using tamoxifen-enriched feed, in a total of 22 mice. The mice were split into two study groups: 15 in a prophylactic study and 7 in a therapeutic pilot study.

In the prophylactic study, eight treatment mice received three TetMYB vaccinations at weeks 7, 9, and 11. Tamoxifen was given to the treatment and control mice at week 13.

 

The seven mice in the therapeutic pilot study were given tamoxifen at week 9 and subsequently monitored via colonoscopy weekly. Once the presence of adenoma was identified, mice received six doses of TetMYB and four doses of anti-PD1 antibody.

In both the prophylactic and therapeutic study, the mice survival rates were higher than expected. In the prophylactic study, the treatment groups’ median survival time was 356 days, nearly double the control group (183 days). More impressively, all mice in the therapeutic group were alive at 235 days.

“The mice were only expected to live for a couple of days or weeks. But, about 50% of them, they lived for more than 2 years,” said Dr. Pham. “Additionally, when the cured mice from the original study were later rechallenged with the same treatment, it was immediately rejected, thus proving there is an immune memory induced by the vaccine.”

With the positive results of the mouse trial, Dr. Pham spoke to the ongoing human clinical trial and the future of this vaccine.

 

“Currently, we are conducting a first-in-human phase 1 clinical trial,” stated Dr. Pham. “The next phase of evolution for our vaccine, which I will also be presenting at DDW, is testing our vaccine as an anti-adenoma vaccine.” Adenomas account for nearly 80% of bowel cancers, according to Dr. Pham.

Should the safety data from the phase 1 trial prove the vaccine to be safe, a follow-up clinical trial looking at high-risk populations would be the next step.

ilacy@mdedge.com

A novel vaccine may provide a breakthrough treatment option in colorectal and other cancers.

“We [researchers] at the Peter MacCallum Cancer Centre in Melbourne, Australia, have developed a new, DNA-based vaccine, which we call TetMYB, for the treatment of MYB-overexpressing cancers such as colorectal, adenoid cystic carcinoma, and breast cancer, to name a few,” Toan Pham, MD, of the Peter MacCallum Cancer Centre, said in a media briefing in advance of the annual Digestive Disease Week^® conference.

The immunotherapy approach described by Dr. Pham involves combining the TetMYB vaccine, which boosts the immune system, and an antibody, BGB-A317, that helps enhance the effectiveness of the vaccine.

luiscar/Thinkstock

The vaccine is administered in the skin where it is taken up via the dendritic cells, which then migrate to the lymph glands where they transfer the vaccine to the cytotoxic T cells, which target and kill cancerous tissues. When these cytotoxic T cells interact with tumor cells, they often encounter countermeasures from the tumors that attempt to inactivate the immune cell by binding to the PD-1 receptor on the cytotoxic T cell. This is why the BGB-A317 antibody is so important. It will bind to the PD-1 receptor, which blocks the PD-L1/L2 ligand on the tumor cell from binding to the T cell, rendering its cytotoxic effects useless. This “immune checkpoint” allows the cytotoxic T cells to function normally, and lyse the tumor cells.

“The research we are presenting at DDW involves testing this approach in mouse models, which we had previously published. In our studies, tumors in the mice responded very well to the treatment and cancer was cured in about half of them,” stated Dr. Pham.

The study is really composed of two smaller studies that looked at colonic adenoma, induced using tamoxifen-enriched feed, in a total of 22 mice. The mice were split into two study groups: 15 in a prophylactic study and 7 in a therapeutic pilot study.

In the prophylactic study, eight treatment mice received three TetMYB vaccinations at weeks 7, 9, and 11. Tamoxifen was given to the treatment and control mice at week 13.

 

The seven mice in the therapeutic pilot study were given tamoxifen at week 9 and subsequently monitored via colonoscopy weekly. Once the presence of adenoma was identified, mice received six doses of TetMYB and four doses of anti-PD1 antibody.

In both the prophylactic and therapeutic study, the mice survival rates were higher than expected. In the prophylactic study, the treatment groups’ median survival time was 356 days, nearly double the control group (183 days). More impressively, all mice in the therapeutic group were alive at 235 days.

“The mice were only expected to live for a couple of days or weeks. But, about 50% of them, they lived for more than 2 years,” said Dr. Pham. “Additionally, when the cured mice from the original study were later rechallenged with the same treatment, it was immediately rejected, thus proving there is an immune memory induced by the vaccine.”

With the positive results of the mouse trial, Dr. Pham spoke to the ongoing human clinical trial and the future of this vaccine.

 

“Currently, we are conducting a first-in-human phase 1 clinical trial,” stated Dr. Pham. “The next phase of evolution for our vaccine, which I will also be presenting at DDW, is testing our vaccine as an anti-adenoma vaccine.” Adenomas account for nearly 80% of bowel cancers, according to Dr. Pham.

Should the safety data from the phase 1 trial prove the vaccine to be safe, a follow-up clinical trial looking at high-risk populations would be the next step.

ilacy@mdedge.com

A novel vaccine may provide a breakthrough treatment option in colorectal and other cancers.

“We [researchers] at the Peter MacCallum Cancer Centre in Melbourne, Australia, have developed a new, DNA-based vaccine, which we call TetMYB, for the treatment of MYB-overexpressing cancers such as colorectal, adenoid cystic carcinoma, and breast cancer, to name a few,” Toan Pham, MD, of the Peter MacCallum Cancer Centre, said in a media briefing in advance of the annual Digestive Disease Week^® conference.

The immunotherapy approach described by Dr. Pham involves combining the TetMYB vaccine, which boosts the immune system, and an antibody, BGB-A317, that helps enhance the effectiveness of the vaccine.

luiscar/Thinkstock

The vaccine is administered in the skin where it is taken up via the dendritic cells, which then migrate to the lymph glands where they transfer the vaccine to the cytotoxic T cells, which target and kill cancerous tissues. When these cytotoxic T cells interact with tumor cells, they often encounter countermeasures from the tumors that attempt to inactivate the immune cell by binding to the PD-1 receptor on the cytotoxic T cell. This is why the BGB-A317 antibody is so important. It will bind to the PD-1 receptor, which blocks the PD-L1/L2 ligand on the tumor cell from binding to the T cell, rendering its cytotoxic effects useless. This “immune checkpoint” allows the cytotoxic T cells to function normally, and lyse the tumor cells.

“The research we are presenting at DDW involves testing this approach in mouse models, which we had previously published. In our studies, tumors in the mice responded very well to the treatment and cancer was cured in about half of them,” stated Dr. Pham.

The study is really composed of two smaller studies that looked at colonic adenoma, induced using tamoxifen-enriched feed, in a total of 22 mice. The mice were split into two study groups: 15 in a prophylactic study and 7 in a therapeutic pilot study.

In the prophylactic study, eight treatment mice received three TetMYB vaccinations at weeks 7, 9, and 11. Tamoxifen was given to the treatment and control mice at week 13.

 

The seven mice in the therapeutic pilot study were given tamoxifen at week 9 and subsequently monitored via colonoscopy weekly. Once the presence of adenoma was identified, mice received six doses of TetMYB and four doses of anti-PD1 antibody.

In both the prophylactic and therapeutic study, the mice survival rates were higher than expected. In the prophylactic study, the treatment groups’ median survival time was 356 days, nearly double the control group (183 days). More impressively, all mice in the therapeutic group were alive at 235 days.

“The mice were only expected to live for a couple of days or weeks. But, about 50% of them, they lived for more than 2 years,” said Dr. Pham. “Additionally, when the cured mice from the original study were later rechallenged with the same treatment, it was immediately rejected, thus proving there is an immune memory induced by the vaccine.”

With the positive results of the mouse trial, Dr. Pham spoke to the ongoing human clinical trial and the future of this vaccine.

 

“Currently, we are conducting a first-in-human phase 1 clinical trial,” stated Dr. Pham. “The next phase of evolution for our vaccine, which I will also be presenting at DDW, is testing our vaccine as an anti-adenoma vaccine.” Adenomas account for nearly 80% of bowel cancers, according to Dr. Pham.

Should the safety data from the phase 1 trial prove the vaccine to be safe, a follow-up clinical trial looking at high-risk populations would be the next step.

ilacy@mdedge.com