ASCO 2016: Natural Killer Cell-Based Therapies in Blood Cancers

Veronika Bachanova, MD

As part of our coverage of the annual American Society of Clinical Oncology conference being held June 3^rd to June 7^th in Chicago, we are speaking today with Veronika Bachanova about using immunotherapy, including natural killer cell-based therapies and novel stimulatory agents to boost immunity for blood cancers. Dr. Bachanova is a hematologist who treats patients with blood cancers and an associate professor of medicine, in the division of hematology, oncology, and transplantation at the University of Minnesota, Dr. Bachanova gave a talk, What We Have Not Heard About the Role of Immunotherapy in Hematologic Malignancies on Friday, June 3^rd at the meeting.

-Interviewed by Anna Azvolinsky, PhD

OncoTherapy Network: First, could you provide a short overview of the different types of immunotherapies that are currently being tested in various hematological malignancies?

Dr. Bachanova: Sure. The concept of immunotherapy involves the idea that cancer cells can be recognized and effectively killed by a functional immune system. So, there are two different ways to think about this. One is how we remove the brakes, which cancer cells develop to be protected against the immune destruction and that is the area of checkpoint inhibitors. The other way to look at this is to ask how we can stimulate and really, kick in and start the immune system so it is more efficient in eliminating the cancer. We have been interested in this second concept for the past many years and using one of the effectors of the immune system, natural killer cells.

NK cells are white cells in our blood that normally are able to eliminate malignantly transformed cells, but they are normally inhibited when they recognize our selves and the loss of self allows the NK cells to be more active. We learned that one of the ways, and this is a conceptual demonstration of efficacy, that one of the ways NK cells can work is if we use donor NK cells from the related donor and infuse those into patients with refractory AML [acute myeloid leukemia], some patients will achieve a complete remission, so this is effectively a cellular therapy. And we have run a number of clinical trials and showed that infusions are safe and that they lead to remissions in about 30% to 50% of patients. So, with some improvements in the technology, we have seen improvements in almost half of the cohort. And the NK cells need cytokines to survive and we are currently using the cytokine IL-15, which is a very potent immune cytokine that allows the cells to persist and grow in patients for a short period of time.

OncoTherapy Network: We’ve heard a lot about Immune checkpoint antibodies, and particularly those targeting the PD-1 receptor and PD-L1 ligand which have been well-studied in solid tumors and these are now also being tested in various blood cancers. And you just gave an example. Is there another example of a therapy, a different type of immunotherapy that is showing efficacy for a lymphoma or leukemia, or perhaps where there is promising data from preclinical models?

Dr. Bachanova: So, other than the cell therapies, which are certainly complex and more difficult to expand widely, we are looking into more of an off-shelf engagers of the immune system. One example is blinatumomab [Blincyto], which is already approved molecule that links T cells with a B-cell tumor because it targets CD19 and this bispecific T-cell engagers, BITEs, have proved to be effective to treat acute lymphoblastic leukemia and are currently also being tested for B-cell lymphoma. We have good and strong preclinical data and we are developing similar bispecific antibodies targeting natural killer cells. We call these BIKEs and TRIKES and these are bi- and tri- and even tetraspecific antibodies that have small molecules that are linking the effector cells with a tumor cell to mediate immune killing. So we are very excited about the preclinical data of these BIKE and TRIKE antibodies. 

OncoTherapy Network: Has there been anything particularly surprising about any of the data thus far on these types of immunotherapies for blood cancers?

Dr. Bachanova: Well, we are learning that the standard biomarkers may not apply to immunotherapies. For example, the chemorefractory leukemias which are linked with mutations, such as FLT3 and others, can still very well respond to immunotherapies such as NK cell therapies. So we initially looked for new biomarkers and prognostic factors which would allow us to select patients who have a better chance to respond. But it will not be the standard or conventional factors.

OncoTherapy Network: What are we still missing and need to understand about the role of immunotherapy for hematological malignancies? 

Dr. Bachanova: I believe that this is a new era in oncology, of immunotherapies, and we are just scratching the surface in understanding of how to use them and how to eventually combine different immunotherapies, particularly combinations of activating cytokines or cellular products with checkpoint inhibitors, to stimulate the immune system from both ends. Also, we need to better understand the safety profile and the dosing and how to use these therapies, in what sequence to allow the best treatment results.

OncoTherapy Network: Thank you so much for joining us today, Dr. Bachanova.

Dr. Bachanova: You are most welcome.