Dr. Krish Patel is a CLL and lymphoma researcher and doctor at Swedish Hospital, Seattle, WA. CLL is a lymphoma, and so research in related B cell lymphomas is important for us to understand.
We caught up in Orlando, FL at ASH 2019 to discuss his research on the frontier of a new type of therapy for CLL, bispecific antibodies.
- Our native immune system is excellent at controlling cancer when it is working normally, so why not modify it in a therapeutic setting as needed.
- In CLL, the immune system has become dysregulated and does a poor job controlling cancer.
- There are multiple therapeutic options for re-activating the immune system in CLL and other cancers.
- Monoclonal antibodies or mAbs, such as rituximab, have already revolutionized the treatment of CLL and other lymphomas. In CLL, most mAbs bind to a protein marker on the cancer cells (CD20) that alerts the immune system to the target.
- Antibodies are Y-shaped.
- Bispecific antibodies attach to both the target cancer cell using CD20 found on all B cells, including cancerous CLL cells on one arm of its Y, and to T cells using CD3 found on T cells on the other arm.
- This has the effect of bringing the target, the CLL cell, and its killer, the T cell close together.
- This is similar to what killer CAR-T cells do where the cells themselves are genetically re-engineered to attach to the target cells.
- Bispecific antibodies have several potential advantages over CAR-T:
- They are “off the shelf” and therefore more available.
- Hematologists are already very familiar with managing infusions of antibodies.
- As with CAR-T, side effects include cytokine release syndrome (CRS) and neuro events, but they tend to be milder.
- Efficacy data has yet to be reported in CLL, but there has been success in one case of Richter’s Transformation and in patients that had failed CAR-T. This is very encouraging as these patients are short on options.
Using the immune system is likely to be part of any cocktail to ultimately eradicate our CLL.
For more on CAR-T therapy see out CAR-T section of the website.
For more of an introduction to different immunotherapies including some more basic information on monoclonal antibodies, please see my article here.
Here is my cartooned simple explanation of bispecific antibodies.
And finally, here is Dr. Pagel’s interview with Dr. Schuster from ASH 2019 on bispecific antibodies.
Please enjoy the video of my ASH 2019 interview with Dr. Patel.
If you want to read the original ASH 2019 abstract, you will find it @ Preliminary Safety and Anti-Tumor Activity of XmAb13676, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia.
If you are interested in the trial Dr. Patel referenced: Study to Evaluate Safety and Tolerability of XmAb13676 in Patients With CD20-expressing Hematologic Malignancies, here it is on Clinicaltrials.gov. The trial is now open for CLL, Richter’s, and other lymphoma patients.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.