This is part two of a two-part series on the role of Adoptive Cell Therapies.
Part 2: Adoptive Cell Transfer and CAR-T Therapies
In December, we interviewed Dr. David Bajor, an oncologist at Case Western Reserve University in Ohio to learn more about Adoptive Cell Therapies. This blog is part two which aims to understand more specifically the role of CAR-T cell therapies and their promise in colorectal cancer research and treatment. Before reading part two, be sure to check out part one!
1) Why have CAR-T trials been successful in liquid tumors such as lymphoma, but not solid tumors like colorectal cancer?
Solid tumors like colorectal cancer are behind liquid malignancies in CAR-T approaches because of the nature of the therapy. CAR-T’s are designed with an antibody attached to the internal part of a T cell receptor. This artificial receptor is able to identify certain cancers by the proteins on their surface.
In myeloma cells, for example, there are unique markers on the outside of these cancer cells which are consistent from patient to patient and CAR-T’s can be designed to target these specific molecules. There are fewer of these unique markers that we have identified in solid tumors like colorectal cancer (CRC), making it more difficult to design successful CARs (chimeric antigen receptor).
The farthest research has progressed for CAR-T therapies in solid tumors is with carcinoembryonic antigens (CEA). CEA is a molecule we follow for cancer patients that can serve as a marker of disease. It is displayed on the outside of a cancer cell and can be attacked by a CAR, however, not everyone makes CEA or to the degree that it can be targeted.
Another reason that Adoptive Cell Transfer (ACT) may be less successful in solid cancers is the way the tumors grow in the body. In solid tumors, cancer cells grow together in a mass. In hematological malignancies (leukemia, lymphoma, myeloma) the cancer cells are more easily encountered by immune cells because they typically occupy the same space (bloodstream, bone marrow, lymph nodes) and they do not form large masses as often.
Researchers around the country and the world are looking for ways to make immunotherapy a bigger component in the treatment of CRC. We are studying ACT, checkpoint inhibitors, and ways of changing the tumor microenvironment to make existing and future treatments work better.
Understanding the biology of cancer and its interaction with the immune system has come a long way, just in the past 10 years but we’re just scratching the surface. Our patients inspire us to keep making discoveries and continue developing new treatments as rapidly as we can.
6) What are the future areas of CAR-T cell research that patients should know about?
One thing that may come together in the next five to ten years is combining CAR- T therapies with checkpoint inhibitors and newer immune modulating agents that will help existing Adoptive Cell Transfer enter a solid tumor’s microenvironment and be more helpful in combination than by themselves. This is something that many people are actively working on.
Some studies like this have taken place, primarily in tumors where CAR-T’s are already being used, especially in combination with nivolumab or pembrolizumab because we see a dampening of an adoptive t-cell strategy.
For example, there was a case report of a patient who had had an adoptive transfer and initially responded to therapy, however they biopsied the tumor and showed that PD-L1 was upregulated. When they used a PD-1 inhibitor in combination with the CAR-T therapy, it continued to work.
5) What should patients know about these types of therapies when making treatment decisions?
Right now all of these therapies are experimental and they are typically only offered at a few institutions around the country. Most patients have to be in very good clinical condition to be eligible due to the logistics of these types of clinical trials. Still, I would encourage patients to talk to their doctors about these studies as they are some of the most exciting trials in current clinical research.
We certainly have a lot of work to do but it’s an exciting time and I think patients and physicians should be optimistic about what’s coming next.
Although there have been fewer studies in CRC of CAR-T treatments than other disease types, there are research studies ongoing that may open doors to new breakthroughs. Many of those for late-stage MSS CRC patients can be found in the Fight CRC clinical trial finder!