2023 Outlook of CAR T-Cell Therapy for Solid Tumors

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of blood cancers like leukemia, lymphoma, and multiple myeloma. Now, researchers are exploring its potential to treat solid tumors as well. Despite the success of CAR T cells in blood cancers, they have not been approved for general use in solid tumors, and their effectiveness has been limited by the heterogeneity of tumor antigens and the hostile microenvironment around the tumor. However, recent research has found ways to overcome these barriers.

In non-small cell lung cancer, targeted agents and surgeries can reduce the size of the tumor, but drug-tolerant persister cells that remain can lead to recurrence of the cancer tumor. Researchers have found that CAR-based cellular therapy directed at cell surface proteins expressed on drug-tolerant persister cells could more effectively delay the emergence of fully drug-resistant cells than targeted agents alone.

Small cell lung cancer is also difficult to treat, and each subtype has different proteins in the membrane surrounding the cancer cell. Researchers have found that targeting these various proteins with specific cellular therapies, such as CAR T, seems to be more effective than a one-size-fits-all treatment.

A Phase I multicenter trial indicates that for patients with advanced kidney cancer, an off-the-shelf type of CAR T cell therapy shows promise. The T cells used to manufacture the CAR T cells are donated by healthy donors, modified to target a protein, called CD70, commonly expressed in kidney cancer. In the trial, cancer seemed to respond to the treatment, even at relatively low doses, and the safety profile has been manageable.

Additionally, researchers are exploring the destruction of cancer-associated fibroblasts (CAFs) to fight tumors. CAFs are cells in the microenvironment around the tumor that promote tumor growth and immune evasion. Researchers have found that CAR T cells that target a protein called fibroblast activation protein-alpha (FAP) expressed on CAFs can reduce tumor growth and increase survival in animal models.

Despite these challenges, researchers are continuing to make progress in developing CAR T-cell therapies for solid tumors. Here's what's next in CAR T cells for solid tumors:

Identifying new targets: One of the biggest challenges in CAR T-cell therapy for solid tumors is identifying targets that are specific to cancer cells and not expressed on healthy tissues. Researchers are continually searching for new targets, and recent advances in genomics and proteomics are helping to speed up the process. For example, researchers are looking at neoantigens, which are unique proteins that are expressed on the surface of cancer cells. Because neoantigens are not expressed on healthy cells, they are a promising target for CAR T-cell therapy.
Enhancing T cell function: Another challenge in CAR T-cell therapy for solid tumors is the hostile microenvironment that surrounds the tumor. This microenvironment can include immunosuppressive cells, cytokines, and other factors that can inhibit the function of T cells. Researchers are working on ways to enhance the function of T cells in the tumor microenvironment. For example, they are using nanoparticles to deliver cytokines directly to the T cells, which can help to boost their function.
Combining therapies: CAR T-cell therapy is often used in combination with other therapies, such as checkpoint inhibitors or chemotherapy. Combining therapies can help to overcome some of the challenges of CAR T-cell therapy for solid tumors. For example, checkpoint inhibitors can help to remove the immunosuppressive cells that are present in the tumor microenvironment, which can enhance the function of CAR T cells. Chemotherapy can also help to create a more favorable microenvironment for CAR T cells by reducing the number of immunosuppressive cells.
Developing new CAR T-cell designs: Finally, researchers are continually developing new CAR T-cell designs that can improve the efficacy of the therapy. For example, they are working on CAR T cells that can secrete cytokines, which can help to recruit other immune cells to the site of the tumor. They are also working on CAR T cells that can target multiple antigens, which can reduce the risk of antigen escape. Antigen escape occurs when cancer cells lose the antigen that is targeted by the CAR T cells, which can render the therapy ineffective.

Each of the key players in the cell and gene therapy space is using different technologies to develop their therapies. For example, Novartis and Gilead are both using CAR-T technology, while bluebird bio is using a lentiviral vector-based gene therapy approach.

Novartis is well-known for its CAR-T therapy Kymriah, which is used to treat certain types of blood cancers. In addition to Kymriah, Novartis is also developing a number of other cell and gene therapies for the treatment of solid tumors, including its CAR-T therapy CT103A, which is in early-stage development for the treatment of solid tumors.
Gilead Sciences is the company behind the CAR-T therapy Yescarta, which is used to treat certain types of lymphoma. Gilead is also developing a number of other cell and gene therapies for the treatment of solid tumors, including its CAR-T therapy KTE-X19, which is in late-stage development for the treatment of mantle cell lymphoma.
Bristol Myers Squibb Co has made significant investments in the cell and gene therapy space. The company's main cell therapy program is its CAR-T therapy Breyanzi, which is used to treat certain types of non-Hodgkin lymphoma. Bristol Myers Squibb is also developing a number of other cell and gene therapies for the treatment of solid tumors, including its CAR-T therapy bb21217, which is in early-stage development for the treatment of multiple myeloma.
bluebird bio Inc is focused on developing gene therapies for the treatment of rare genetic diseases and cancer. The company's main cell therapy program is its CAR-T therapy idecabtagene vicleucel, which is in late-stage development for the treatment of multiple myeloma. bluebird bio is also developing a number of other cell and gene therapies for the treatment of solid tumors, including its CAR-T therapy bb2121, which is in early-stage development for the treatment of multiple myeloma.

BioIntel360 believes that CAR T-cell therapy for solid tumors is a rapidly evolving field. While there are still many challenges to overcome, researchers are making significant progress in developing CAR T-cell therapies that can effectively target solid tumors. By identifying new targets, enhancing T cell function, combining therapies, and developing new CAR T-cell designs, researchers are working to unlock the full potential of this promising therapy.