Both leukemia and glioblastoma cancers are alike in the sense of how they haunt our population today: their devastating diagnosis, fatality rates, and overall struggle that most people associate with cancer. Yet, the two diseases also share another aspect in common which is currently helping to make a more positive impact in their respective research fields, and it involves a pursued method of treatment called Chimeric antigen receptor (CAR) T-cell immunotherapy.
Why does CAR T-cell immunotherapy work better for leukemia than for glioblastoma cancer, although it is used as a means of treatment in both cases? That is the question currently plaguing researchers, since, according to the Leukemia Lymphoma Society, the five year survival rate of patients with Leukemia has almost quadrupled to 65.8 percent in recent years [9] whereas the National Brain Tumor Society states that the five year survival rate for glioblastoma patients is only 6.8 percent [10].
Although some CAR T-cell therapy treatments for leukemia are currently FDA approved in the United States, it is more difficult for scientists to generate an equivalently effective treatment for glioblastoma. After pondering why these large discrepancies are the case, researchers have found that the answers may lie in the complex cell networks and interstitial fluid flow involved in a glioblastoma multiforme tumor microenvironment which do not exist in leukemia cancers.
Leukemia and CAR T-Cell Immunotherapy
Leukemia is a type of blood cancer concentrated in the immune system’s white blood cells, one of the most basic parts of the human body [1 & 7]. Within the lymphatic system, cancer cells can travel around a patient’s body easily, and it often exists in a free-moving environment without other obstacles besides immune system cells due to the nature of it being a blood cancer. Therefore, it is fitting to use CAR T-cell therapy to counteract the effects of the proliferation of blood cancers, as the treatment itself involves using one’s own white blood T-cells to the patient’s advantage by biomedical engineering them to target cancer cells more effectively than usual [7].
In addition, unlike glioblastoma multiforme, leukemia cancer isn't particularly originative in solid tumors. Leukemias generally do not form solid tumors, whereas brain cancers most often do. This is part of the reason why leukemia has fared better when it comes to immunotherapy methods so far and in its survival rate mentioned earlier in the article; Biomedically engineered immunotherapy cells only need to travel along the lymphatic system to maintain their designed purpose, whereas in glioblastoma multiforme or other solid tumor cancers, the tumor microenvironment components counter and provide obstacles for researchers trying to biomedically engineer CAR T-cells to properly target intended cancerous tumor cells.
Glioblastoma Multiforme and CAR T-Cell Immunotherapy
So now that we know about leukemia cancer, what cells make up a glioblastoma multiforme tumor that makes it very different? Along with the tumor cells themselves, there is the perivascular niche (cells around or near blood vessels), necrotic (dead cell) area growth, vascular tissue blood networks, lymphocytes (types of white blood cells), and more - segments of which are characterized by different types of fluids that make it so hard to navigate when it comes to creating treatments to alleviate the conditions of the cancer and treat patients in the real world [2].
Jon Hamilton, a correspondent for NPR’s Science Desk, claims that “even the three-pronged treatment approach of surgery, radiation and chemotherapy usually isn't enough to eliminate a glioblastoma [11].” Because glioblastoma directly affects the glial cells of the brain - fluid-like cells which surround neurons that have a consistency like glue - it is difficult for CAR T-cells to navigate glioblastoma tumor microenvironments unlike the relatively obstacle-free one of leukemia.
Yet, it is only recently that a new method of analysing the interstitial tumor flow (the transport of fluids which are known to aid in cancer cell migration) within a brain tumor has been proposed as a way to increase the receptivity of glioblastoma patients to CAR T-cell therapy where immune system cells are biomedically engineered to kill cancer cells [3 & 4]. CAR T-cell’s ability to function has never been analyzed in regard to fluid flow and the complex microtumor environments that exist within the unique networks of glioblastoma multiforme tumors.
Although originating in one’s immune system cells, CAR T-cells have the potential to reach solid tumors like glioblastoma multiforme through the blood brain barrier and through interstitial fluid flow within the tumor despite interferences [6]. Within the glioblastoma tumor microenvironment, there are niches which contain neural stem cells, astrocytes, necrotic zones, and signaling pathways which are ultimately connected in a larger scale to the interstitial fluid flow system where cells are transferred through fluid in the extracellular matrix [8].
According to researchers, the“IFF [interstitial fluid flow] is involved in increasing proliferation, triggering invasion of tumor cells, and altering the surrounding microenvironment to promote cancer progression” [5]. Interstitial fluid flow therefore, unlike in leukemia immunotherapy, is important to target through new biophysics research techniques in order to see how it affects glioblastoma cancer’s proliferation.
Conclusion
Figuring out how to analyze the interstitial fluid flow of a glioblastoma tumor would be vital in allowing researchers to engineer CAR T-cells more efficiently and accurately to the specific disease, rather than relying on the success of leukemia immunotherapy treatments in the past. As a result, with new technology that can measure the microtumor environment of glioblastoma in a new way, it may be possible in the future to predict rate, volume, and complexity relationships within interstitial fluids in order to more fully understand the resistance CAR T-cells face once within a patient’s system [4]. Consequently, more biochemical and biophysical research must be done on ways to alter CAR T-cell immunotherapy regarding different pathways so that medical researchers can increase the survival rate of glioblastoma multiforme patients, and create another treatment with a more promising outcome.