What You Should Know about Adoptive Cell Therapy (ACT): Part 1

Read time: 4 minutes

• What are ACT therapies?
• Research that has been done on ACT therapies before
• ACT therapies for colorectal cancer (CRC)

This is part one of a two-part series understanding Adoptive Cell Therapies (ACT) and the future of these therapies for patients.

As a patient, caregiver, or individual interested in colon or rectal cancer research, you’ve probably heard of a variety of acronyms such as ACTs, CAR-Ts or TILs thrown around in the past few months. That’s because science in this area is progressing fast, and these types of therapies are showing promise in cancer research.

We interviewed Dr. David Bajor, an oncologist at Case Western Reserve University in Ohio to help us understand what these terms mean, what type of prior success they’ve had, and where they’re heading for colorectal cancers.

What does Adoptive Cell Transfer mean? What are the different types of ACTs?

There are several types of adoptive cell therapies, all of which involve infusing living immune cells into a patient. Most of these cells are derived from the patients themselves but in certain circumstances the transferred cells could come from another patient or donor.

• Chimeric Antigen Receptor –T-cells (CAR-T): These are T-cells (lymphocytes) which are harvested from the blood and then genetically modified to have a specific receptor, a chimeric receptor, that can recognize proteins on the outside of cancer cells and attack those cells. The chimeric receptor is roughly composed of an antibody fragment and the intracellular portion of the normal T-cell receptor.
• Tumor Infiltrating Lymphocyte (TIL) infusions:  These are given to a patient in the hope of allowing a better systemic immune response at other metastatic sites. When a solid tumor is surgically removed, the lymphocytes, a type of white blood cells, are taken out and preserved, and allowed to divide outside of the body through stimulation with lymphocyte growth factors.  This larger number of cells which may have been responding to the tumor can now be sorted by T-cell type and given back to the patient (as an infusion) in the hope of allowing a better systemic immune response at other metastatic sites.
• T-cell Receptor Modified T-cells: These are like CAR-T cells except that the genetically modified protein is a T-cell Receptor which recognizes different types of tumor antigens. Such a receptor could theoretically be made to recognize almost any portion of any cancer specific protein.
• Natural Killer (NK) cell therapies: NK cells are given to patients. These cells have different anti-cancer properties than T-cells, specifically, they can recognize tumors that have lost the ability to display internal antigens, which is the main way T-cells can identify a tumor as foreign and attack it. NK cells have the ability to look at a cell and see if it’s no longer expressing the internal antigen, therefore destroying the tumor.

What research has been conducted on ACT therapies previously?

There have been successful trials of CAR-T cells in leukemia, lymphoma, and myeloma.  These have been very exciting and have led to commercial approval for these therapies.

Are adoptive cell transfer therapies promising for colorectal cancer research? Where do we stand with ACT research in CRC?

There have been fewer studies in CRC of CAR-T treatments than some other malignancies however there have been some interesting studies. There have been studies of a CEA CAR-T.  There are ongoing TIL trials at the NCI with Dr. Steven Rosenberg which have shown interesting results. Additionally, my institution, Case Western Reserve University, has an ongoing study of NK cell infusions in patients with colorectal cancer.

What should patients know about the future of immunotherapy?

The way forward in immunotherapy is to use all of the targets we have at our disposal. We’ve spent the last 20 years looking at targets within a cancer and their genetic drivers. We’ve gotten really good, especially at targeting KRAS mutant and wild-type colon cancers and finding drugs for them, but moving forward we’re going to be able to use different targets in the immune system that more patients have and hopefully make those therapies beneficial to everybody. Just like we sequence a tumor, we may be looking at strengths and weaknesses in people’s immune system to figure out which immunotherapies will work better for certain people.

Stay tuned for part two of this blog series to learn more about the future of Adoptive Cell Transfer therapies for colorectal cancer!

In the meantime, you can read more about immunotherapy and colorectal cancer here!