Feature

Remote-controlled immunotherapy system shows potential as noninvasive cancer treatment

Peter Yingxiao Wang

Engineering researchers at University of California, San Diego, developed a remote-controlled cancer immunotherapy system.

The ultrasound-based system is designed to noninvasively control genetic processes in T cells to recognize and kill cancer cells.

Chimeric antigen receptor T-cell therapy is becoming a paradigm-shifting therapeutic approach for cancer treatment,” Peter Yingxiao Wang, MD, professor of bioengineering in the department of bioengineering at Institute of Engineering in Medicine at University of California, San Diego, said in a press release.

“However, major challenges remain before CAR T-cell-based immunotherapy can become widely adopted,” Wang added. “For instance, the nonspecific targeting of CAR T cells against nonmalignant tissues can be life threatening. This work could ultimately lead to an unprecedented precision and efficiency in CAR T-cell immunotherapy against solid tumors, while minimizing off-tumor toxicities.”

HemOnc Today spoke with Wang about how this system was developed, how it works, the early efficacy it has demonstrated and the research underway to validate its effectiveness.

 

Question: How did you develop this system?

Answer: We tried to combine our ultrasound system with these genetic sensors and transducers so that we can mechanically activate cells using ultrasound to drive the engineered gene to produce proteins, which allow the CAR T cells to recognize tumors.

 

Q: How does the system work?

A: We have several components that allow for the application of the signal from the ultrasound. Basically, there is a microbubble with air inside and liquid outside. When the ultrasound is used, it will cause the microbubble to shrink and expand. This will create an oscillating stretch when we physically attach these microbubbles to the cell surface, via sticky proteins coated on the microbubbles so that these bubbles can stick to the cell surface. These will then trigger the opening of sensors on the cell surface. These sensors will allow calcium to go in to the cell which will activate a phosphatase enzyme to induce the gene expression and hence desired protein production.

 

Q: Can you describe the early sense of efficacy and safety?

A: At this time, the efficacy is actually less optimal, because when we deliver the gene, only 20% or less of the cells were infected. This, however, can be potentially improved with newer technology that we are further exploring. As for safety, this ultrasound-guided activation with confined space and precise timing offers a highly safe approach.

 

Q: What type of additional research is underway or needs to be conducted to validate its effectiveness?

A: In our current study, we demonstrate how this technology can work. Our next step is to continue this research in more animal models. Right now, we are conducting an animal study to examine the efficiency and safety. I am expecting that within a year or a year and a half, these studies will be completed. Then we can start the preclinical and clinical trials in humans.

 

Q: What type of need could this fill or benefits might it offer?

A: This will have huge benefits, particularly with cancer immunotherapy. Right now, CAR T cells are doing well against blood tumors. There is a very convenient antigen, CD19, that can eradicate blood tumor cells. However, for solid tumors, this is more difficult.

 

Q: How long might it be until something like this actually could be adopted in practice?

A: Although the proof of concept of the technology has been established, it will take time to optimize the efficiency and safety of the approach in animal studies, and apply for human subjects. Even under optimistic conditions, it is expected that 6 to 8 years may be needed before a commercial product can be available for clinical practices.

 

Q: Is there anything else that you would like to mention?

A: The integration of new technology and engineering approach with medicine could provide unprecedented opportunities for the treatment of various diseases. – by Jennifer Southall

 

For more information:

Peter Yingxiao Wang, MD, can be reached at University of California, San Diego, SERF 255, 9500 Gilman Drive, La Jolla, CA 92093-0435; email: yiw015@eng.ucsd.edu.

 

Disclosure: Wang reports no relevant financial disclosures.

Peter Yingxiao Wang

Engineering researchers at University of California, San Diego, developed a remote-controlled cancer immunotherapy system.

The ultrasound-based system is designed to noninvasively control genetic processes in T cells to recognize and kill cancer cells.

Chimeric antigen receptor T-cell therapy is becoming a paradigm-shifting therapeutic approach for cancer treatment,” Peter Yingxiao Wang, MD, professor of bioengineering in the department of bioengineering at Institute of Engineering in Medicine at University of California, San Diego, said in a press release.

“However, major challenges remain before CAR T-cell-based immunotherapy can become widely adopted,” Wang added. “For instance, the nonspecific targeting of CAR T cells against nonmalignant tissues can be life threatening. This work could ultimately lead to an unprecedented precision and efficiency in CAR T-cell immunotherapy against solid tumors, while minimizing off-tumor toxicities.”

HemOnc Today spoke with Wang about how this system was developed, how it works, the early efficacy it has demonstrated and the research underway to validate its effectiveness.

 

Question: How did you develop this system?

Answer: We tried to combine our ultrasound system with these genetic sensors and transducers so that we can mechanically activate cells using ultrasound to drive the engineered gene to produce proteins, which allow the CAR T cells to recognize tumors.

 

Q: How does the system work?

A: We have several components that allow for the application of the signal from the ultrasound. Basically, there is a microbubble with air inside and liquid outside. When the ultrasound is used, it will cause the microbubble to shrink and expand. This will create an oscillating stretch when we physically attach these microbubbles to the cell surface, via sticky proteins coated on the microbubbles so that these bubbles can stick to the cell surface. These will then trigger the opening of sensors on the cell surface. These sensors will allow calcium to go in to the cell which will activate a phosphatase enzyme to induce the gene expression and hence desired protein production.

 

Q: Can you describe the early sense of efficacy and safety?

A: At this time, the efficacy is actually less optimal, because when we deliver the gene, only 20% or less of the cells were infected. This, however, can be potentially improved with newer technology that we are further exploring. As for safety, this ultrasound-guided activation with confined space and precise timing offers a highly safe approach.

 

Q: What type of additional research is underway or needs to be conducted to validate its effectiveness?

A: In our current study, we demonstrate how this technology can work. Our next step is to continue this research in more animal models. Right now, we are conducting an animal study to examine the efficiency and safety. I am expecting that within a year or a year and a half, these studies will be completed. Then we can start the preclinical and clinical trials in humans.

 

Q: What type of need could this fill or benefits might it offer?

A: This will have huge benefits, particularly with cancer immunotherapy. Right now, CAR T cells are doing well against blood tumors. There is a very convenient antigen, CD19, that can eradicate blood tumor cells. However, for solid tumors, this is more difficult.

 

Q: How long might it be until something like this actually could be adopted in practice?

A: Although the proof of concept of the technology has been established, it will take time to optimize the efficiency and safety of the approach in animal studies, and apply for human subjects. Even under optimistic conditions, it is expected that 6 to 8 years may be needed before a commercial product can be available for clinical practices.

 

Q: Is there anything else that you would like to mention?

A: The integration of new technology and engineering approach with medicine could provide unprecedented opportunities for the treatment of various diseases. – by Jennifer Southall

 

For more information:

Peter Yingxiao Wang, MD, can be reached at University of California, San Diego, SERF 255, 9500 Gilman Drive, La Jolla, CA 92093-0435; email: yiw015@eng.ucsd.edu.

 

Disclosure: Wang reports no relevant financial disclosures.

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