How CAR Cellular Therapies are Pushing Boundaries in Cancer Treatment and Personalized Healthcare

Recently, research has shown that cutting-edge cancer treatments are saving lives. Companies dedicated to researching and developing new ways to fight cancer are pushing the boundaries in personalized healthcare and cancer treatment one innovative step at a time.

Brooke Hirsch, Ph.D. holds a doctorate in molecular biology from the University of Colorado and works as a Senior Practice Manager with Actalent. She has extensive experience in molecular biology and is familiar with the pharmaceutical and biotechnological industry, making her a great resource for information on chimeric antigen receptor (CAR) cellular therapy. In this Q&A, Brooke Hirsch, Ph.D. addresses commonly asked questions around CAR cell therapy, the science behind it, and the challenges that arise when utilizing this treatment.

Q: What is cellular therapy?

A: Cellular therapy is the process of using cells in various medical treatments. Blood transfusions, red cell and platelet transfusions, bone marrow transplants, and even organ transplants are all forms of cell therapy.

Q: What are chimeric antigen receptors (CARs)?

A: CARs, or chimeric antigen receptors, are genetically engineered receptor proteins that enable immune response cells to target specific proteins more efficiently.

Q: What is CAR-T cell therapy?

A: Our immune system is designed to fight cancer and it does so on a regular basis, but cancer can grow at a faster rate than the immune system can fight it. Additionally, cancer cells are similar to a virus – they adapt. This means that while the immune system may be equipped to fight off cancer for a certain amount of time, the cancer cells will eventually morph to avoid the immune response and increase their chances of survival.

This is where CAR-T cell therapy comes in. To put it simply, CAR-T cell therapy is a form of immunotherapy that uses a patient's T cells – a part of the immune system – to fight cancer. CAR-T cell therapy consists of collecting blood from a patient, separating the T cells, genetically modifying them to produce cancer-fighting CAR receptors that target specific proteins, and infusing them back into the patient.

Currently, the FDA has approved CAR-T cell therapy for various types of lymphoma in adults and patients up to the age of 25 with lymphoblastic leukemia.

Q: What is CAR-M therapy?

A: Similar to how CAR-T cell therapy works with T cells, CAR-M therapy is focused on utilizing cells called macrophages. Macrophages are large, phagocytic cells found in stationary form in the tissues or as a mobile white blood cell. Like cancer, tumors reach a point where they can grow at an equal or faster rate than the immune system can fight them. CAR-M therapy takes a patient's macrophages and engineers them with a specific CAR gene that enables them to target specific cells, particularly tumor cells.

CAR-M therapy provides an entirely new method through which we can fight cancer and malignant tumors.

Q: What is the difference between CAR-T cell and CAR-M therapies?

A: CAR-T cell therapy has been proven effective against blood cancers such as lymphoma and leukemia, but it has yet to be proven effective against solid tumors. CAR-M therapy, on the other hand, is effective against solid tumors.

Penn State is just one of the many organizations dedicating time and resources to better understand, innovate, and improve CAR-T and CAR-M therapies. Macrophages interact with tumor cells in a way that t-cells cannot; they can penetrate and live inside the tumor cells. Macrophages are even able to use the byproducts of tumor cells to generate a stronger response from the immune system, supporting the fact that when engineered with CARs, macrophages can be incredibly effective in reducing and eliminating solid tumors.

Q: What are the advantages of using cellular therapies like the ones mentioned?

A: There are so many advantages to cellular therapy using CARs, some of which I think are yet to be seen. Both CAR-T cell and CAR-M therapies involve taking one's cells and engineering them to target a threat (like cancer) better than they would have before. The engineered cells are then returned to the patient they were removed from, boosting the patient's immune response. The process of manufacturing these batches of uniquely engineered cells is the embodiment of personalization in healthcare. This customized treatment is more effective than a standardized treatment because it has been specifically engineered and designed to meet the needs of each individual.

Really, cellular therapy like this completely redefines our current understanding of personalized healthcare and customized treatment manufacturing.

Q: What are the challenges and limitations of this kind of cell therapy?

A: For one, CAR cell therapies are costly and time consuming. The process of engineering one's cells with CARs can cost hundreds of thousands of dollars, meaning that even though this kind of technology is life-changing, the cost makes it inaccessible to a large part of the population. It can also take weeks to have the cells taken, modified, and returned to the patient. An off-the-shelf option could be available to the patient in a much smaller period of time, but it would not have the personalized component the therapy has in its current process.

Another challenge for companies looking to expand their work in CAR cellular therapy is the lack of access to professionals with relevant experience. This is still a new treatment, meaning the only professionals out there with experience in CAR cellular engineering are generally working for a small number of companies competing in the same space. Without experienced professionals, expansion in this form of cellular therapy will be slow.

Q: What role does Actalent play in addressing these challenges and pushing innovation in CAR cellular therapy?

A: Working with an engineering and sciences services provider can help any company looking to expand their expertise by building a flexible workforce that is capable of expediting business development goals.

Employers are facing the toughest labor market in decades, and companies looking for STEM talent are coming up especially short. Working with a services provider like Actalent can help bridge that gap. With our network of highly skilled specialists, scientists, and engineers, Actalent can help companies increase their bandwidth to take on additional projects such as R&D efforts centered around boosting understanding of CAR cellular therapy. Actalent can be the link between a company's aspirations and what is possible.

Q: Where is this industry looking to improve and expand in the future?

A: This is still a new practice, and we have a lot yet to learn. One of the biggest challenges moving forward will be finding a way to make this treatment less costly so it is accessible to more people. Progress will rely on whether companies can find the right professionals to drive the manufacturing and technological advancements needed to expedite the process and reduce costs.

There is so much more progress left to make. Actalent is excited to be a part of that progress and to push the boundaries of cellular therapy when it comes to cancer treatment, manufacturing, and personalized healthcare.

_{Originally published date: February 5, 2020}